Repercussions of chronic protein-calorie malnutrition on glucose homeostasis in the rat

Summary The characteristics, progressivity and reversibility of the changes in glucose homeostasis brought about by chronic protein-calorie malnutrition were studied in the rat. Four-week-old male rats received a control diet (15% protein) or a low-protein diet (5% protein) until the age of 28 weeks. Other rats received the low-protein diet until 12–15 weeks, and then the control diet. In malnourished rats, fasting plasma glucose levels and both fasting and fed plasma insulin levels were lower than in control rats. At the age of 15 weeks, tolerance to oral glucose was slightly poorer, whereas tolerance to intravenous glucose was slightly better in rats receiving the low-protein diet than in control rats. During both tests the insulin response of malnourished rats was severely blunted. This inhibition largely exceeded the small decrease in their pancreatic insulin reserves. Similar results were obtained when the same test was repeated 9 weeks later. If the rats were transferred from a low-protein to a control diet for these 9 weeks, the changes in glucose tolerance were partially corrected, but the insulin response remained inhibited. Though hepatic glycogen stores were increased in malnourished rats, i. v. glucagon or arginine caused a smaller rise in plasma glucose levels than in control rats. The insulin response was also impaired and, unlike the glucose response, was not restored by 6 weeks on a control diet. The hypoglycaemia induced by intravenous insulin was more sustained in malnourished than in control rats, but this abnormality was corrected by refeeding a control diet for 6 weeks. The results thus show that chronic protein-calorie malnutrition in the rat severely impairs insulin secretion, but only mildly alters glucose tolerance, likely because of an associated high sensitivity to insulin. These changes do not aggravate with time and are only partially reversed by several weeks on a control diet.     

Search for Extrapancreatic Effects of New Oral Hypoglycemic Agent A-4166: 1. Oral Glucose Tolerance Tests in Normal and Hereditary Insulin Resistant Rats

OBJECTIVE: To test the effect of new oral hypoglycemic compound A-4166 on insulin secretion during oral glucose challenge in normal and hereditary non-obese, hypertriglyceridemic, insulin resistant and hypertensive rats fed either a normal or high fat diet. METHODS: The rats used were 15 weeks old males of Wistar Charles River strain (controls) and Wistar-derived hereditary hypertriglyceridemic (hHTg) rats of our own colony. They were fed either basal (12 cal% of fat) or high fat diet (70 cal% fat). After 3 weeks of feeding the above diets, the oral glucose tolerance tests (2 g/kg) were carried out in unrestrained conscious rats kept in special metabolic cages after overnight fasting and ten minutes after the administration of A-4166 (100 mg/kg) or placebo by the stomach tube. Plasma glucose, triglycerides, free fatty acids and insulin levels were measured by routine analytical methods. RESULTS: High fat diet feeding resulted in an increase in fasting plasma insulin in both rat strains, while fasting plasma glucose in high fat diet fed animals remained unchanged as compared to those fed basal diet. No differences in the fasting FFA levels were found. The glucose area under curve (AUC) did not differ between the two strains used and high fat diet resulted in a higher glucose AUC in both strains. The administration of A-4166 improved the glucose tolerance in all animals, namely in those fed the basal diet. Insulin AUC showed very similar pattern in both rat strains proving the stimulatory effect of A-4166 on insulin secretion during an oral glucose challenge. High fat feeding resulted in an impairment of insulin action, but the administration of A-4166 restored the antilipolysis in both strains to the normal range. CONCLUSIONS: The previously reported hypoglycemic action of A-4166 resulting from the increased insulin secretion was confirmed. Moreover, some beneficial action of A-4166 on antilipolysis in vivo was demonstrated.     

Long term improvement of glucose homeostasis by vanadate in obese hyperinsulinemic fa/fa rats

The trace element vanadium (V) exerts insulin-like effects in vitro and lowers blood glucose in streptozotocin-diabetic rats. The present study examined whether V can also improve glucose homeostasis in genetically obese, insulin-resistant rats. Na3VO4 was administered for 3 months in water and food to Zucker fa/fa rats. Since these V rats reduced their food intake by about 30% compared to controls (C), one group of untreated rats was pair-fed (P-F) with V rats. In the fed state, the insulin/glucose ratio was lower in V rats than in P-F or C rats, merely because of a decrease (approximately 50%) in plasma insulin levels. Tolerance to oral glucose was improved in V rats only; the integrated glucose response was 30% lower than that in P-F or C rats. Insulin levels were also lower in V rats, but the integrated response was not consistently decreased. During an iv glucose tolerance test, the glucose disappearance rate was 50% higher in V rats than in the other two groups. An iv arginine test clearly showed that B-cell responsiveness was not increased in V rats. Insulin sensitivity, assessed by insulin-induced hypoglycemia, was similar in V and P-F rats and slightly better than that in C rats. In conclusion, oral vanadate produces a sustained improvement of glucose homeostasis by an insulin-like, largely body weight-independent mechanism in genetically insulin-resistant rats.     

Oral supplementation with physiological doses of leptin during lactation in rats improves insulin sensitivity and affects food preferences later in life

We have previously described that neonate rats supplemented with physiological doses of oral leptin during lactation become more protected against overweight in adulthood. The purpose of this study was to characterize further the long-term effects on glucose and leptin homeostasis and on food preferences. Neonate rats were supplemented during lactation with a daily oral dose of leptin or the vehicle. We followed body weight and food intake of animals until the age of 15 months, and measured glucose, insulin, and leptin levels under different feeding conditions: ad libitum feeding, 14-h fasting, and 3-h refeeding after fasting. An oral glucose tolerance test and a leptin resistance test were performed. Food preferences were also measured. Leptin-treated animals were found to have lower body weight in adulthood and to eat fewer calories than their controls. Plasma insulin levels were lower in leptin-treated animals than in their controls under the different feeding conditions, as was the increase in insulin levels after food intake. The homeostatic model assessment for insulin resistance index was significantly lower in leptin-treated animals, and the oral glucose tolerance test also indicated higher insulin sensitivity in leptin-treated animals. In addition, these animals displayed lower plasma leptin levels under the different feeding conditions and were also more responsive to exogenous leptin administration. Leptin-treated animals also showed a lower preference for fat-rich food than their controls. These observations indicate that animals supplemented with physiological doses of oral leptin during lactation were more protected against obesity and metabolic features of the metabolic syndrome.     

Glucose tolerance after portacaval shunt in liver cirrhosis

The liver plays a key role in glucose homeostasis and insulin metabolism. Altered glucose and insulin levels in peripheral blood are common findings in chronic liver disease. The aim of the present study was to investigate the effect of surgical portosystemic shunt on plasma glucose and insulin responses to glucose administration in a group of cirrhotic patients. For this purpose 10 cirrhotic subjects (8 males and 2 females) aged 42 to 65 years underwent an oral glucose tolerance test (OGTT, 75 g), and an intravenous glucose tolerance test (IVGTT, 0.33 g/kg) before and after undergoing a side-to side portocaval anastomosis (PCS). 6 noncirrhotic, nondiabetic patients matched for sex, age and body weight who underwent abdominal vascular surgery served as controls. In cirrhotic subjects, the PCS resulted in: increased plasma glucose and insulin levels during OGTT; decreased C-peptide level during OGTT; unmodified plasma glucose and insulin concentrations during IVGTT. In control subjects the abdominal surgery did not affect plasma glucose and insulin responses to oral or intravenous glucose loads. These results suggest that in cirrhotic subjects surgical portocaval shunt results in: deterioration of oral but not intravenous glucose tolerance, due to an escape of ingested glucose from the liver; increased peripheral insulin response to oral glucose administration as a consequence of reduction in hepatic removal of the hormone; and decreased pancreatic response to oral glucose due possibly to a greater feed back inhibition of beta-cell. These events seem to be a consequence of the shunt per se and not of a deterioration of hepatocellular function.     

Glucose tolerance and insulin resistance in the JCR:LA-corpulent rat: effect of miglitol (Bay m1099).

A standardized meal tolerance test (MTT) using 5 g rat chow provides a sensitive index of insulin and glucose metabolism in the insulin-resistant, hyperinsulinemic, hypertriglyceridemic, and atherosclerosis-prone JCR:LA-corpulent (cp) strain of rats. The MTT revealed differences in insulin/glucose metabolism that were not evident in either an intravenous (IVGTT) or intraperitoneal (IPGTT) glucose tolerance test. The glycemic response of control rats to a 5-g carbohydrate test meal containing miglitol (Bay m1099) was sharply reduced, with a 50% effective dose (ED50) of 36.4 +/- 7.5 mg/100 g food. At a dose of 60 mg/100 g food, the plasma glucose curve was flat and indistinguishable from that found in the nonfed state. The plasma insulin response was similarly reduced, with an ED50 of 42.8 +/- 14.8 mg/100 g food. Obese male rats were treated with miglitol at 60 mg/100 g food from 6 to 12 weeks of age. Treated rats had a significantly reduced food consumption and lower body weight at 12 weeks of age (P < .05). The treatment resulted in no significant changes in serum lipid concentrations. When subjected to the MTT using control (non-miglitol-containing) food, treated rats demonstrated markedly improved insulin sensitivity, with a greatly reduced insulin response, which may reflect an improved hepatic glucose metabolism. The results confirm that miglitol is highly effective in this obese insulin-resistant animal model. It reduced postprandial glycemic and insulin responses, and on long-term treatment, it improved glucose and insulin metabolism. These beneficial metabolic changes suggest that miglitol may have vascular protective effects in insulin-resistant states.     

Importance of preabsorptive insulin release on oral glucose tolerance: studies in pancreatic islet transplanted rats

The role of preabsorptive (cephalic phase) insulin release in oral glucose tolerance was investigated using diabetic rats treated by intraportal transplantation of isogenic islets. This early neurally mediated phase of insulin release has been shown to be absent in such rats. When the body weight of transplanted rats was normalised, glucose tolerance tests (GTTs) were performed in the unstressed state using permanent cardiac catheters. Transplanted rats had a normalised intravenous GTT, whereas, as we have shown previously, their oral GTT remained clearly pathological. During both tests peripheral insulin levels were decreased compared with controls. While during intravenous GTT the onset of insulin release occurred as early in transplanted rats as in controls, during oral GTT there was a clear delay, probably because of the absence of the cephalic phase. Re-establishment of normal preabsorptive insulin levels was attempted by a small intravenous insulin injection during this period. This resulted in a transient increase in peripheral insulin levels, which, at two minutes after glucose ingestion, gave values similar to those found in controls at that time. This small insulin injection caused a marked improvement of the oral GTT which was most evident after exogenous insulin had disappeared from the blood. While the injection did not affect the 60 minute incremental insulin area, the glucose area was decreased by 50%, to a value not significantly different from that of control rats. The cephalic phase of insulin release appears, therefore, to be one important factor in the control of glycaemia during food intake. Its absence plays a major role in the pathological oral glucose tolerance of diabetic rats treated by intraportal islet transplantation.     

Involvement of endogenous glucagon-like peptide-1(7-36) amide on glycaemia-lowering effect of oligofructose in streptozotocin-treated rats

We have evaluated the influence of oligofructose (OFS), a fermentable dietary fibre, on glucose homeostasis, insulin production and intestinal glucagon-like peptide-1 (GLP-1) in streptozotocin-treated diabetic rats. Male Wistar rats received either i.v. streptozotocin (STZ; 40 mg/kg) or vehicle (CT); one week later, they were fed for 6 weeks with either the standard diet (STZ-CT), or with a diet containing 10% oligofructose (STZ-OFS); both diets were available ad libitum. In a second set of experiments (duration 4 weeks), a supplemental group of food-restricted rats (STZ-Res) receiving a similar intake as CT rats, was added. OFS improved glucose tolerance and reduced food intake as compared with STZ-CT rats in both the post-prandial state and after an oral glucose tolerance test. After 6 weeks, portal and pancreatic insulin concentrations were doubled in STZ-OFS rats. Food restriction improved these parameters when compared with STZ-CT rats, but to a lesser extent than in the STZ-OFS group. We have shown that OFS treatment increased portal and colonic GLP-1(7-36) amide levels and doubled colonic proglucagon and prohormone convertase 1 mRNA levels; both OFS and food restriction lowered ileal GLP-1(7-36) amide levels as compared with levels in STZ-CT rats. We propose that OFS, through its fermentation in the colon, promotes the expression and secretion of colonic peptides, namely GLP-1(7-36) amide, with beneficial consequences on glycaemia, insulin secretion and hyperphagia in diabetic rats.     

Exercise training normalizes glucose metabolism in a rat model of impaired glucose tolerance

The purpose of this study was to characterize an animal model of impaired glucose tolerance produced by streptozocin treatment of rats (45 mg/kg, intravenously [i.v.]) and selection of animals with plasma glucose concentrations less than 150 mg/dL. In addition, we determined the effects of physical training on glucose tolerance and metabolism in these animals. During 10 weeks of monitoring, it was determined that these animals have nearly normal plasma glucose concentrations; however, they have an impaired glucose tolerance when challenged with an oral glucose load. They also have normal fasting insulin, free fatty acid, and triglyceride concentrations, normal body weight and food consumption patterns, and normal rates of skeletal muscle glucose uptake, but impaired basal and insulin-stimulated glucose metabolism in isolated adipose cells. Ten weeks of exercise training normalized both the impaired glucose tolerance and adipose cell function present in the untrained streptozocin-treated rats. Low-dose streptozocin treatment of rats with appropriate selection of animals based on plasma glucose concentrations appears to be an excellent model of impaired glucose tolerance for studies of factors affecting insulin resistance and altered glucose metabolism.     

Effect of lifelong high- or low-salt intake on blood pressure, left ventricular mass and plasma insulin in Wistar rats

BACKGROUND: Salt restriction is recommended for hypertension treatment to reduce blood pressure, but its effect on some risk factors is still a matter of discussion. The aim of this study was to observe the effect of a long period of salt restriction or overload on blood pressure, left ventricular mass (LVM), kidney mass (KM), glucose tolerance, and plasma insulin. METHODS: Male Wistar rats were fed from weaning with a low-salt diet (LSD) or a high-salt diet (HSD) until 72 weeks of age. After 48 weeks, the diets were changed in half of the rats: HSD until 48 weeks and then LSD (LHSD) and LSD until 48 weeks and then HSD (HLSD). Body weight, blood pressure, electrolyte excretion, creatinine clearance, plasma renin activity, LVM, KM, and intravenous glucose tolerance test with insulin determinations were evaluated. RESULTS: Blood pressure, LVM and KM were higher on the HSD than on the LSD. Blood pressure was lower on the LHSD than on the HLSD. There were no differences in LVM and KM on the LHSD compared with the HLSD. The relationship between area under the curve (AUC) of insulin and glucose during the intravenous glucose tolerance test was higher on the LSD. No differences were detected in AUC between the two groups of rats whose diet were inverted with 48 weeks of age. CONCLUSIONS: A chronic HSD increases blood pressure, LVM, and KM and a chronic LSD increases plasma insulin in response to a glucose challenge in aging rats. The hypotensive effect of salt restriction is not modified by a previous long period on a HSD.     

Different diabetogenic response to moderate doses of streptozotocin in pregnant rats, and its long-term consequences in the offspring

Diabetes during pregnancy results in congenital malformations and long-term postnatal diseases. Experimental models are still needed to investigate the mechanism responsible for these alterations. Thus, by the administration of different doses of streptozotocin (STZ) (0, 25, 30, or 35 mg/kg body weight, intravenous) at the onset of pregnancy in rats, the present study sought an appropriate animal model for this pathology. At day 6 of pregnancy, plasma glucose was progressively higher with an increasing STZ dose, and in rats receiving the 35-mg dose, 2 subgroups were detected: some animals had plasma glucose levels above controls but below 200 mg/dL (mildly diabetic, MD), whereas others had levels above 400 mg/dL (severely diabetic, SD). At day 20 of pregnancy, the MD rats had normal glycemia, but after an oral glucose load (2 g/kg body weight), plasma glucose increased more and insulin increased less than in controls. The SD rats maintained their hyperglycemia and had a greatly impaired oral glucose tolerance. At day 20, fetuses of SD dams were fewer, weighed less, and had enhanced plasma glucose and triglycerides and decreased insulin, whereas those from MD dams did not differ from controls. At birth, newborns from MD dams had higher body weight, plasma insulin, and liver triglycerides as well as total body lipid concentrations than controls, and on day 21, remained macrosomic and showed higher plasma glucose and liver triglyceride concentrations. At 70 days of age, offspring of MD dams had impaired oral glucose tolerance but normal plasma insulin change in the case of females, whereas plasma insulin increased less in males. These alterations were manifest more in those offspring from dams that had >50% macrosomic newborns than in those from dams that had <50% macrosomic newborns. In conclusion, whereas our MD rats mimic the changes taking place in gestational diabetic women and show the long-term risk of macrosomia, the SD rats are more similar to uncontrolled diabetics. Thus these two rat models, obtained with moderate amounts of STZ, could be used to study the pathophysiological consequences of these different diabetic conditions.     

Hypersecretion of proinsulin in thyrotoxicosis

Summary The plasma insulin, C-peptide and proinsulin concentrations were investigated in thyrotoxic patients and in normal controls after an overnight fast, during a 36 h fasting period, an intravenous glucose tolerance test and an oral glucose tolerance test. The main finding was a significantly raised concentration of proinsulin in plasma of patients with thyrotoxicosis. After an overnight fast the plasma proinsulin was 0.048±0.005 pmol/ml in 15 thyrotoxic patients compared with 0.023±0.012 pmol/ml in 15 euthyroid controls. A twofold rise of plasma proinsulin concentration was also found in thyrotoxic patients during a prolonged fast, and during intravenous and oral glucose tolerance tests. The immunoreactivity of proinsulin in the insulin radioimmunoassay gave rise to slightly elevated concentrations of immunoreactive insulin in thyrotoxic patients in all the conditions investigated. When insulin values were corrected for proinsulin crossreactivity, they were similar in euthyroid controls and thyrotoxic patients. The concentration of plasma C-peptide was not significantly altered in thyrotoxic patients during intravenous and oral glucose tolerance tests.     

Improvement in glucose tolerance as a result of enhanced insulin sensitivity during electroacupuncture in spontaneously diabetic Goto-Kakizaki rats

We studied whether electroacupuncture (EA) applied on the abdomen improved glucose tolerance in the Goto-Kakizaki (GK) rat, a genetic model of type 2 diabetes mellitus. Male GK rats and nondiabetic Wistar rats were studied under pentobarbital anesthesia. Blood samples were drawn from the ventral tail artery during the fasting stage and after a glucose load (0.5 g/kg). Electroacupuncture (15 Hz, 10 mA) was performed for 90 minutes during both the fasting and intravenous glucose tolerance test (IVGTT) periods. A hyperinsulinemic euglycemic clamp was also carried out to assess glucose uptake during EA. A significant decrease in fasting blood glucose and an increase in plasma insulin levels were observed during the fasting period in GK rats treated with EA. Blood glucose levels after glucose load were also significantly lower in GK rats treated with EA compared with controls. The homeostasis model assessment index during IVGTT indicated an improvement in insulin sensitivity in GK rats treated with EA, whereas glucose infusion rate during hyperinsulinemic clamp was increased significantly during EA. The present study demonstrated that EA improved hyperglycemia in the fasting stage with a marked increase in plasma insulin levels. Electroacupuncture also restored impaired glucose tolerance during an IVGTT in GK rats by enhancing insulin sensitivity.     

Oral selenate improves glucose homeostasis and partly reverses abnormal expression of liver glycolytic and gluconeogenic enzymes in diabetic rats

Summary Selenium is a trace element that exerts certain insulin-like actions in vitro. In this study, we evaluated its in vivo effects on the glucose homeostasis of rats made diabetic and insulin-deficient by streptozotocin. Na₂SeO₄ was administered ad libitum in drinking water and/or food for 10 weeks. The elevated plasma glucose levels (~ 25 mmol/l) and glucosuria (~ 85 mmol/day) of untreated rats were decreased by 50 and 80%, respectively, by selenate treatment. The beneficial effect of selenate was also evident during oral and intravenous glucose tolerance tests: the integrated glucose responses were decreased by 40–50% as compared to those in untreated rats. These effects were not due to an increase in plasma insulin levels. Compared to non-diabetic rats, pancreatic insulin reserves were reduced by more than 90% in treated and untreated diabetic rats. The hepatic activities and mRNA levels of two key glycolytic enzymes, glucokinase and l-type pyruvate kinase were blunted in diabetic rats. They increased ~ two- to threefold after selenate treatment, to reach 40–75% of the values in non-diabetic rats. In contrast, elevated activity and mRNA levels of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase, were reduced by 40–65% after selenate administration. Since selenate induced a moderate decrease in body weight due to an anorexigenic effect, we checked that there was no improvement of glucose homeostasis or hepatic glucose metabolism in an additional group of calorie-restricted diabetic rats, which was weight-matched with the selenate group. In addition, no obvious toxic side-effects on the kidney or liver were observed in the rats receiving selenate. In conclusion, selenate induces a sustained improvement of glucose homeostasis in streptozotocin-diabetic rats by an insulin-like action, which involves partial correction of altered pretranslational regulatory mechanisms in liver metabolism.Abbreviations GK Glucokinase - l-PK l-type pyruvate kinase - PEP phosphoenolpyruvate - PEPCK phosphoenolpyruvate carboxykinase - C non-diabetic control rats - D untreated diabetic rats - WM weight-matched diabetic rats - Se selenatetreated diabetic rats - OGTT oral glucose tolerance test - IV-GTT intravenous glucose tolerance test - STZ streptozotocin - SSC sodium saline citrate - SSPE sodium saline phosphate ethylenediamine tetraacetic acid - GLUT2 glucose transporter isoform 2     

Effects of dietary inorganic trivalent chromium (Cr3+) on the development of glucose homeostasis in rats

Inorganic chromium (Cr3+) is classified as an essential trace element on the basis of a small dietary requirement for the maintenance of efficient glucose homeostasis. The present study has carefully scrutinised this claim by examining food intake, body weight gain, glycosylated haemoglobins, plasma glucose and insulin concentrations, glucose tolerance and insulin sensitivity in two groups of Wistar rats fed either a Cr3+-deficient (0.03 mg/kg) or Cr3+-containing (1 mg/kg) diet for 32 days from weaning at 3 weeks. At 53 days of age, control rats weighed 183 +/- 7 g (body weight gain 155 +/- 6 g, mean +/- SEM) and consumed 17 +/- 1 g diet/rat/day. Glycosylated haemoglobins, plasma glucose and plasma insulin were 2.5 +/- 1%, 6.4 +/- 0.3 mmol/l and 1.2 +/- 0.3 ng/ml, respectively. Compared with control rats, the rats fed the Cr3+-deficient diet consumed the same total amount of diet and exhibited up to a maximum 40% decrease in the chromium content of selected tissues at 53 days of age. At no time during the study did food intake, body weight, glycosylated haemoglobins or plasma concentrations of glucose and insulin differ between the two groups of rats. Furthermore, body weight gain and both glucose tolerance and insulin sensitivity were identical at 50-53 days of age. These results cast doubt on the significance of dietary trivalent chromium for the maintenance of glucose homeostasis in healthy animals.     

Hyperinsulinemia and glucose tolerance in obese rats with lesions of the ventromedial hypothalamus: dependence on food intake and route of administration

This study was performed to investigate the consequences of developing obesity on glucose homeostasis in animals showing hyperphagia plus vagal hyperinsulinemia and rats that were normophagic and hyperinsulinemic. Male rats were lesioned in the ventromedial hypothalamus (VMH) and kept either under ad libitum or absolute (oral or intragastrical) pair-feeding conditions for 4 weeks. Hyperphagic rats, as well as normophagic VMH rats, became obese, but only ad lib-fed obese rats displayed glucose intolerance to intravenous (IV) glucose infusions. Orally pair-fed VMH rats also showed normal oral and intragastric glucose tolerance, but in intragastrically fed VMH animals and controls, oral and intragastric glucose tolerance was decreased. These results indicate that (1) obesity as a consequence of VMH lesions is not dependent on hyperphagia, confirming earlier reports, and also independent of the ingestion of bulk meals. (2) beta-cell release of insulin to IV glucose infusion is not sufficient when hyperphagia and vagally mediated hyperinsulinemia coincide, and is therefore dependent on several factors; and (3) oral glucose intolerance develops when preabsorptive reflexes are blunted, irrespective of whether the animals were hyperinsulinemic or not.     

Cameroon local diet-induced glucose intolerance and dyslipidemia in adult Wistar rat

It has been hypothesised that glucose intolerance or diabetes can be induced in rodents by a hypercaloric-fat diet or a hypercaloric-sucrose diet. This study was designed to examine the effects of a high-fat diet (HFD: carbohydrates 35-40% kcal, fat 50-55% kcal, protein 10-15% kcal) and a high-sucrose diet (HSD: carbohydrates 65-70% kcal, fat 25-30% kcal, protein 10-15% kcal) compared to a normal or standard diet (ND: carbohydrates 50-55% kcal, fat 15-20% kcal, protein 25-30% kcal) on fasting plasma glucose, glucose tolerance test, plasma triglycerides, plasma cholesterol, body weight, food and water consumption in male Wistar rats. After 4 months, weight gain, plasma triglycerides level, fasting plasma glucose and water intake were significantly elevated (p<0.05) in all test groups when compared to the control group. Total HDL and LDL cholesterol levels were significantly elevated (p<0.05) in the HFD group, whereas the HDL level was significantly lower in the HSD group associated with an atherogenic index significantly elevated (p<0.05) when compared to the control group. After 16 weeks of dietary treatment, an oral glucose tolerance test (OGTT) showed a significant increase in plasma glucose levels after 2-4 h of glucose challenge in all test groups. During the experiment, it was noticed that important weight gain observed in all dietary test groups was associated with a significant low (p<0.05) food consumption. The above results suggest that dietary nutrients contained in these hypercaloric diets might have an effect on insulin action and therefore, might contribute to the development of glucose intolerance and type 2 diabetes. These results also suggest that, in addition to their diabetogenic effect, these hypercaloric diets might probably have an atherogenic effect and could be use in a long-term study to induce type 2 (non-insulino-dependant) diabetes mellitus.     

Skeletal muscle magnesium content is correlated with plasma glucose concentration in patients with essential hypertension treated with lisinopril or bendrofluazide

The association between change in glucose metabolism and change in skeletal muscle magnesium (Mg) concentration induced by antihypertensive treatment was evaluated in 37 patients with essential hypertension randomly treated with either lisinopril or bendrofluazide. Before and after 6 months of treatment, skeletal muscle biopsies were performed, glucose tolerance was determined by oral (OGTT) and intravenous glucose tolerance tests (IVGTT), and insulin sensitivity was assessed by the hyperinsulinemic euglycemic clamp technique. An inverse relationship was found between the treatment-induced change in fasting plasma glucose concentration and change in skeletal muscle Mg concentration (r = -0.39, P < .05). However, there was no significant correlation between skeletal muscle Mg content and either insulin sensitivity measured by the hyperinsulinemic euglycemic clamp test or glucose tolerance evaluated by IVGTT and OGTT. In conclusion, an increased circulating glucose concentration was correlated with a decreased Mg concentration in skeletal muscle during antihypertensive treatment. However, the Mg concentration in skeletal muscle did not significantly predict the insulin sensitivity or glucose tolerance.     

Effect of Gymnema sylvestre, R.Br. on glucose homeostasis in rats.

Effect of Gymnema sylvestre, R.Br. (G. sylvestre; GS4) on glucose homeostasis was studied in rats. In the first set of experiments, the acute effect of GS4 was examined in both non-diabetic and streptozocin (30 mg/kg)-induced mildly diabetic rats. Administration of 1 g/kg body weight of GS4 to 18-h fasted non-diabetic rats significantly attenuated the serum glucose response to oral administration of 1 g/kg glucose. The immunoreactive insulin (IRI) response in GS4-administered rats was lower, but not significantly, than that in control rats. In mildly diabetic rats, a 60 min increment in serum glucose concentrations was significantly reduced by GS4 administration. No IRI response was observed in these diabetic rats irrespective of GS4 administration. In the second set of experiments, the chronic effect of GS4 was examined in mildly diabetic rats. Two weeks after the induction of diabetes, the rats were divided into two groups that had similar impairment of glucose tolerance assessed by an oral glucose loading test. The rats were fed for 32-35 days with either a control diet or a diet supplemented with GS4. After 4 weeks, GS4 showed a tendency to reduce the serum glucose concentrations in the fed state and to improve the glucose tolerance. Gain in body weight, food intake, pancreas weight and the pancreatic contents of IRI, protein, amylase and trypsinogen were unaltered in the GS4-treated group compared with the control. These results suggest the usefulness of G. sylvestre in the treatment of certain classes of non-insulin-dependent diabetes mellitus.     

The effect of oral synthetic protease inhibitor (FOY 305) on endocrine pancreas and carbohydrate and lipid metabolism in normal and streptozotocin-induced diabetic rats

The effect of long-term oral synthetic protease inhibitor (FOY 305) administration on fasting blood sugar (FBS), body weight, glucose tolerance, plasma insulin and glucagon levels, pancreatic insulin and glucagon contents, hepatic enzyme activities, and plasma lipids in normal and streptozotocin (STZ)-induced diabetic rats was studied. Normal rats treated with oral FOY 305 for 9 weeks were found to have pancreatic hypertrophy and decreased body weight gain as compared with the untreated normal controls. FBS, glucose tolerance, plasma insulin and glucagon levels, pancreatic insulin and glucagon contents, and plasma lipids were uninfluenced in FOY 305 treated normal rats. STZ-induced diabetic rats treated with oral FOY 305 were found to have decreased FBS for 5 weeks after the beginning of FOY 305 administration as compared with the untreated diabetic controls, whereas at the 7th and 9th week after treatment there was no difference in FBS between FOY 305 treated and untreated diabetic rats. In the metabolic balance observed at the 4th week after treatment, a slight improvement of the diabetic state was found in FOY 305 treated diabetic rats. There was no apparent difference in the blood sugar curve and insulin response following oral glucose load between diabetic rats treated for 7 weeks and untreated diabetic rats. All the rats were sacrificed after 9 weeks of treatment. Diabetic rats treated with oral FOY 305 for 9 weeks showed pancreatic hypertrophy and decreased plasma glucagon level and decreased pancreatic glucagon content as compared with the untreated diabetic controls, whereas there was no difference in body weight, plasma insulin level and pancreatic insulin content between FOY 305 treated and untreated diabetic rats. Furthermore, oral FOY 305 treatment improved hyperlipidemia in STZ-induced diabetic rats and also significantly improved the hepatic pyruvate kinase and phosphoenlpyruvate carboxykinase activities of diabetic rats. These improvements might partly be due to a decreased pancreatic content and secretion of glucagon and/or a direct action of the synthetic PI, FOY 305 to tissues.