Maternal hyperglycemia in pregnant rats: its effect on growth and carbohydrate metabolism in the offspring

Mild hyperglycemia during the last half of pregnancy was achieved by administration of streptozotocin to pregnant rats on the fifth day of gestation. Citrate buffer (vehicle for streptozotocin) was administered to control rats also on the fifth day of gestation. The pups born to the streptozotocin-treated mothers had higher birth weight, pancreatic insulin content, plasma insulin, and C-peptide concentrations compared with pups born to control mothers. The plasma glucose concentrations of the pups were similar between the two groups. The pups who were identified as macrosomic (birth weight greater than 1.7 SD than the mean of the control pups) maintained an accelerated postnatal growth through the first 10 weeks of age in female rats and in the first 3, and at 5 and 6 weeks of age for the male rats. The accelerated growth in the female rats was associated with higher perirenal-ovarian and salpingeal fat weight at 6 weeks. At 10 weeks of age, higher plasma insulin and glucose concentrations were observed following oral glucose challenge in both male and female macrosomic rats than in the control rats. At 12 weeks of age, only the female macrosomic rats showed abnormal glucose response due to peripheral insulin resistance. In the male rats at 12 weeks of age, a higher plasma insulin concentration in the macrosomic group was associated with a normal plasma glucose response to oral glucose challenge. We conclude that mild maternal hyperglycemia in rats resulted in fetal hyperinsulinemia and accelerated fetal growth.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

N-3 fatty acids modulate antioxidant status in diabetic rats and their macrosomic offspring

OBJECTIVE: We investigated the role of dietary n-3 polyunsaturated fatty acids (n-3 PUFA) in the modulation of total antioxidant status in streptozotocin (STZ)-induced diabetic rats and their macrosomic offspring. DESIGN: Female wistar rats, fed on control diet or n-3 PUFA diet, were rendered diabetic by administration of five mild doses of STZ on day 5 and were killed on days 12 and 21 of gestation. The macrosomic (MAC) pups were killed at the age of 60 and 90 days. MEASUREMENTS: Lipid peroxidation was measured as the concentrations of plasma thiobarbituric acid reactive substances (TBARS), and the total antioxidant status was determined by measuring (i) plasma oxygen radical absorbance capacity (ORAC), (ii) plasma vitamin A, E and C concentrations, and (iii) antioxidant enzymes activities in erythrocytes. The plasma lipid concentrations and fatty acid composition were also determined. RESULTS: Diabetes increased plasma triglyceride and cholesterol concentrations, whereas macrosomia was associated with enhanced plasma cholesterol and triglyceride levels, which diminished by feeding n-3 PUFA diet. N-3 PUFA diet also reduced increased plasma TBARS and corrected the decreased ORAC values in diabetic rats and their macrosomic offspring. EPAX diet increased the diminished vitamin A levels in diabetic mothers and vitamin C concentrations in macrosomic pups. Also, this diet improved the decreased erythrocyte superoxide dismutase and glutathione peroxidase activities in diabetic and macrosomic animals. CONCLUSION: Diabetes and macrosomia were associated with altered lipid metabolism, antioxidant enzyme activities and vitamin concentrations. N-3 PUFA diet improved hyperlipidemia and restored antioxidant status in diabetic dams and MAC offspring.     

Effect of acipimox on plasma lipids and glucose/insulin in pregnant rats

To determine how a reduction in maternal hypertriglyceridemia during late pregnancy may affect glucose/insulin relationships, pregnant and virgin rats were orally treated with acipimox, a potent antilipolytic agent. In 20-day pregnant rats receiving 80 mg of acipimox, plasma triglycerides (TG), free fatty acids (FFA), and glycerol decreased more than in virgin rats shortly after the drug (up to 7 hours), when compared with animals treated with distilled water, whereas plasma glucose level was unaffected by the treatment in either group of rats. When acipimox was given every 12 hours from day 17 to day 20 of pregnancy, plasma TG, FFA, and glycerol levels progressively increased, whereas they either decreased or did not change in virgin rats receiving the same treatment, with no effect in plasma glucose levels in either group. Fetal body weight was lower than in controls in 20-day pregnant rats that received acipimox for 3 days. On day 20 of pregnancy, 3 hours after receiving acipimox or distilled water, rats received a 2 g glucose/kg oral load and it was found that the change in plasma glucose was similar in both groups, whereas the increase in plasma insulin was greater in pregnant rats treated with acipimox. However, no difference was found in either variable after the oral glucose load in virgin rats receiving acipimox or distilled water. No differences in plasma glucose levels were found after intravenous (i.v.) administration of insulin in pregnant rats treated or not treated with acipimox. In conclusion, present results show that administration of acipimox during the last days of gestation inhibited lipolysis and decreased fetal weight. Over a short period of time, in pregnant rats, reductions of plasma FFA and TG after acipimox treatment improved the glucose-induced insulin release, but did not seem to have any effect in peripheral insulin resistance.     

Experimental study on diabetes and pregnancy: with special reference to the effects of insulin treatment on fetuses of diabetic dams

Through the development of treatment of diabetes mellitus, diabetic cases of pregnancy have been increasing, and the effects of maternal hyperglycemia and insulin-treated hypoglycemia on the growth and life of fetuses and newborns are becoming very important problems. However, it is difficult for us to investigate the fetuses of human diabetic mothers as experimental models. Although many reports deal with the development of newborns of diabetic mothers and about their secretory changes of insulin and C-peptide reactivity, there have been few reports concerning the effects of severe diabetes on pregnancy and the effects of insulin treatment on fetuses. Concerning experimental animals, there are also few reports about the effects of insulin treatment on diabetic pregnant animals. We conducted the present investigation to determine the effects of insulin treatment on the growth and metabolism of the fetuses of diabetic pregnant rats. Virgin female Wistar rats weighing 200 approximately 300 g were caged overnight with male rats. The mated females were isolated and the gestational age was calculated from noon of this day (zero). Seventeen of 24 pregnant rats received a rapid intravenous injection of 50 mg/kg body weight of streptozotocin (STZ) in 0.4 ml of 0.01 M citrate buffer (pH 4.5) immediately after blood samples were collected through the jugular vein under light ether anaesthesia on the 5th day of gestation. Seven pregnant rats were injected with only 0.4 ml of citrate buffer and served as the controls. These rats were divided into four groups, and each group was named as follows: Normal pregnant rats group (group I, n = 7), diabetic pregnant rats group (group II, n = 6) and insulin-treated diabetic pregnant rats group (group III: plasma glucose level 60 approximately 300 mg/dl, n = 6 and group IV: plasma glucose level below 60 mg/dl, n = 5). Group III and IV rats were treated with a subcutaneous injection of Lente Insulin (from 2 u. to 6 u.) every day from the 13th to the 19th day of gestation. Group II rats were injected with saline every day in the same way. Maternal blood samples were collected under light ether anaesthesia after feeding ad libitum on the 5th and 12th days of gestation. On the 20th day of gestation, the pregnant rats were anaesthetized by an intraperitoneal injection of sodium pentobarbital, and blood samples were collected in the manner stated above. Each fetus and placenta was taken out individually by hysterotomy.(ABSTRACT TRUNCATED AT 400 WORDS)     

Influence of maternal diabetes on fetal rat development: alteration of insulin receptors in fetal liver and lung

The influence of maternal diabetes on fetal development was studied in rats made diabetic by administration of streptozotocin on day 2 of gestation as well as in genetically diabetic BB Wistar rats. A dose of 65 mg streptozotocin/kg produced severe diabetes with plasma glucose levels of approximately 36 mmol/l, this was associated with fetal growth retardation but not fetal hyperinsulinaemia. In contrast, a smaller dose of streptozotocin (45 mg/kg) produced moderate diabetes with plasma glucose levels of approximately 20 mmol/l and was associated with fetal hyperinsulinaemia but only a marginal effect on fetal size. In both groups of diabetic animals, maternal body weight gain was decreased, maternal plasma insulin levels were low and fetal glucose levels were similar. In a small group of genetically diabetic BB rats on insulin therapy the fetuses were macrosomic and hyperinsulinaemic. The specific binding of 125I-labelled insulin to partially purified liver and lung membranes of fetuses of both groups of streptozotocin-induced diabetic rats was significantly lower than the binding to membranes from fetuses of control animals. The specific binding of 125I-labelled insulin to fetal liver and lung membranes from the diabetic BB Wistar rats also appeared to be reduced when compared to tissues from controls. Decreased insulin receptors in fetal lung and liver of diabetic rats suggest a role for insulin in the development of these organs during the fetal and neonatal period.     

Pancreatic hormones in streptozotocin-diabetic rats

Summary Pancreatic polypeptide (PP) levels of plasma and pancreas were studied in the rat after streptozotocin (STZ) injection. In 4 weeks of observation, plasma PP was elevated up to 4 times the control values with marked hyperglycemia and insulinopenia. At 4 weeks, intravenous (i.v.) glucose tolerance tests and i.v. insulin tolerance tests were performed. In the glucose tolerance test, control rats responded with a 10-fold increase in plasma insulin and 15% decrease in plasma PP levels, whereas STZ-diabetic rats produced no increase of plasma insulin and an approximately 50% reduction of plasma PP levels with marked hyperglycemia. In the insulin tolerance test, diabetic rats showed a marked increase in plasma PP levels and less increase in plasma insulin levels than the controls. In diabetic rats, pancreatic insulin levels were reduced to about 3.5% of control, whereas those of somatostatin (SRIF), PP and glucagon were elevated to 8.3, 2.7 and 1.4 times control, respectively. In a morphometric study, islet areas of diabetic rats were seen to be reduced to about 10% of control. With in vitro perfused pancreatic slices, STZ-diabetic pancreas released much more glucagon and PP than control pancreas. Thus, STZ injection in the rat caused marked β-cell damage as well as hyperplasia of SRIF, PP and glucagon cells, with glucagon and PP hypersecretion.     

Pancreatic hormones in streptozotocin-diabetic rats

Pancreatic polypeptide (PP) levels of plasma and pancreas were studied in the rat after streptozotocin (STZ) injection. In 4 weeks of observation, plasma PP was elevated up to 4 times the control values with marked hyperglycemia and insulinopenia. At 4 weeks, intravenous (i.v.) glucose tolerance tests and i.v. insulin tolerance tests were performed. In the glucose tolerance test, control rats responded with a 10-fold increase in plasma insulin and 15% decrease in plasma PP levels, whereas STZ-diabetic rats produced no increase of plasma insulin and an approximately 50% reduction of plasma PP levels with marked hyperglycemia. In the insulin tolerance test, diabetic rats showed a marked increase in plasma PP levels and less increase in plasma insulin levels than the controls. In diabetic rats, pancreatic insulin levels were reduced to about 3.5% of control, whereas those of somatostatin (SRIF), PP and glucagon were elevated to 8.3, 2.7 and 1.4 times control, respectively. In a morphometric study, islet areas of diabetic rats were seen to be reduced to about 10% of control. With in vitro perfused pancreatic slices, STZ-diabetic pancreas released much more glucagon and PP than control pancreas. Thus, STZ injection in the rat caused marked beta-cell damage as well as hyperplasia of SRIF, PP and glucagon cells, with glucagon and PP hypersecretion.     

Potent hypoglycaemic activity of the aqueous extract of Chamaemelum nobile in normal and streptozotocin-induced diabetic rats

The purpose of this study was to investigate the effect of both a single dose and daily oral administration for 15 days of the aqueous extract of the aerial part of Chamaemelum nobile (C. nobile) at a dose of 20mg/kg body weight on blood glucose concentrations and basal insulin levels in normal and streptozotocin-induced diabetic rats (STZ). Single oral administration of C. nobile aqueous extract reduced blood glucose levels from 6.0 +/- 0.3 mmol/l to 4.9 +/- 0.09 mmol/l (P < 0.05) 6h after administration in normal rats and from 21.1 +/- 1.3 mmol/l to 14.5 +/- 0.9 mmol/l (P < 0.001) in STZ diabetic rats. Furthermore, blood glucose levels were decreased from 6.1 +/- 0.06 mmol/l to 4.6 +/- 0.17 mmol/l (P < 0.01) and from 21.1 +/- 1.31 mmol/l to 13.7 +/- 0.9 mmol/l (P < 0.01) in normal and STZ diabetic rats, respectively, after 15 days of treatment. Basal plasma insulin concentrations remain unchanged after treatment in both normal and STZ diabetic rats so the mechanism of this pharmacological activity seems to be independent of insulin secretion. We conclude that the aqueous extract of C. nobile exhibits a significant hypoglycaemic effect in normal and STZ diabetic rats without affecting basal plasma insulin concentrations and support, therefore, its traditional use by the Moroccan population.     

Hypothalamo-hypophysial-thyroid axis in streptozotocin-induced diabetes.

Diabetes mellitus is frequently associated with reduced levels of TSH, PRL, GH, and gonadotropins. In this study we have wanted to determine whether chemically induced diabetes mellitus is associated with a decreased hypothalamic release of TRH. Male rats were made diabetic with streptozotocin (STZ; 65 mg/kg), whereas controls received vehicle. After 2 weeks, STZ diabetic rats had 25% lower body weights, 3.5-fold higher blood glucose, and 40-60% lower plasma TSH, T3, and T4 levels than controls. The plasma T4 dialyzable fraction had increased 2.5-fold in STZ diabetic rats, and the plasma free T4 concentration was similar to that in controls. Thus, treatment with STZ results in decreased plasma TSH and T4 levels, but does not reduce free T4 concentrations. The content of TRH in hypothalami of 2-week STZ diabetic rats was similar to that in controls, but in vitro these hypothalami released less TRH than those of control rats. In 2-week STZ diabetic rats, TRH in hypophysial stalk blood was 30% lower than that in control rats. The in vitro TRH secretion from hypothalami of untreated rats was dependent on the glucose concentrations in the incubation medium; increasing the glucose concentration from 10 to 30 mM did not alter TRH secretion, but basal TRH release increased in the absence of glucose. In conclusion, STZ-induced diabetes in the rat is associated with reduced hypothalamic secretion of TRH, which, in turn, may be responsible for the reduced plasma TSH and thyroid hormone levels. Furthermore, it is suggested that the inhibitory effect of STZ-induced diabetes on TRH secretion is probably not due to hyperglycemia.     

Blood pressure changes associated with hyperinsulinemia or long-standing diabetes mellitus in spontaneously hypertensive rats

We studied the long-term change in blood pressures of spontaneously hypertensive rats (SHR) treated neonatally with streptozotocin (STZ). Two-day-old male SHR were injected intraperitoneally with 37.5–75.0 mg/kg STZ or with vehicle as control. STZ-treated SHR were divided into mildly or severely diabetic groups according to the nonfasting plasma glucose level at age 12 weeks (the former <300 mg/dl, the latter ≧300 mg/dl). In the mildly diabetic group (MD) (n = 5), body weight increased and nonfasting plasma glucose was normalized. At 52 weeks of age, fasting plasma glucose levels were lower than controls owing to hyperinsulinemia, and insulinomas were found in 60% of rats. The systolic blood pressure (SPB) as measured by a tail-cuff method, decreased after 40 weeks, and the mean BP from 44 to 52 weeks (188 ± 4 mmHg) was significantly lower than that in the control group (209 ± 3 mmHg, p < 0.01). In the severely diabetic group (SD) (n = 6), hyperglycemia persisted until 52 weeks, although its severity became less marked. BP in the SD group increased after 36 weeks, and the mean BP from 44 weeks to 52 weeks (224 ± 5 mmHg) was significantly higher than control (p < 0.05). The present study demonstrated that hypertension was ameliorated in SHR associated with hyperinsulinemia, and deteriorated with long-standing diabetes mellitus.     

Effect of Sanguis draxonis (a Chinese traditional herb) on the formation of insulin resistance in rats

Sanguis draxonis (SD) is a Chinese traditional herb that is prescribed for the handling of diabetic disorders. In this study, the effects of an oral administration of SD at dosages of 100, 300, and 500 mg kg(-1) once a day, respectively, on the formation of insulin resistance were investigated in vivo in two models of insulin-resistant rats, HFD rats (high-fat diet-induced insulin-resistant rats) and IILI rats (induced by the intraperitoneal injections of long-acting insulin at dosage of 0.5 U kg(-1) three times daily). The insulin resistance was indicated using the loss of tolbutamide-induced hypoglycemic activity. After the oral administration of SD (300 and 500 mg kg(-1) once a day for 7 days) to HFD rats, both plasma glucose and insulin concentration were decreased significantly, while the hypoglycemic activity of tolbutamide (10 mg kg(-1), i.p.) was significantly enhanced as compared with that of the vehicle-treatment (0.9% saline solution used as vehicle to disperse SD, w/v). Moreover, the formation of insulin resistance in IILI rats had been improved significantly with SD treatment (100, 300, 500 mg kg(-1) once a day for 14 days), but the influence of SD treatment on both plasma glucose and insulin concentration was not observed. For STZ-induced diabetic rats, the action of SD (300 and 500 mg kg(-1) once a day for 14 days) showed more effective on an increase of response to the exogenous short-acting porcine insulin than that of the metformin administrated orally at dosage of 320 mg kg(-1) three times daily. The present studies suggest that an oral administration of SD can increase insulin sensitivity and improve the development of insulin resistance in rats.     

Antidiabetic activity of gossypin, a pentahydroxyflavone glucoside, in streptozotocin-induced experimental diabetes in rats

Background: Most of the currently available oral hypoglycemic drugs for the treatment of diabetes mellitus elicit detrimental side effects. Hence, the search for plant‐derived products for the treatment of diabetes continues. Gossypin, a pentahydroxy flavone glucoside found in the flowers of Hibiscus vitifolius, has many biological properties, including as an antioxidant, anti‐inflammatory and anticancer agent. The aim of the present study was to evaluate the effect of gossypin in streptozotocin (STZ)‐induced experimental diabetes in rats. Methods: Diabetic rats were administered 20 mg/kg per day gossypin orally for 30 days. On the 28th day, rats were subjected to an oral glucose tolerance test. In addition, blood glucose, plasma insulin, hemoglobin, and HbA1c levels were determined, as was the glycogen content of the liver and muscles. Plasma protein and blood urea were also estimated. Results: Oral administration of gossypin to diabetic rats resulted in improved glucose tolerance. Increased blood glucose and HbA1c levels and the reduced plasma insulin and hemoglobin levels in diabetic rats were significantly reversed to near normal after oral administration of gossypin. Furthermore, the glycogen content of the liver and muscles was significantly improved after gossypin treatment of diabetic rats, and plasma protein and blood urea levels were almost normalized. The data obtained in gossypin‐treated rats were comparable with those obtained following gliclazide treatment of rats, a standard reference drug for diabetes. Conclusions: The results of the present study indicate that gossypin has potent antidiabetic activity in STZ‐induced experimental diabetes in rats.     

Characteristic features of insulin secretion in the streptozotocin-induced NIDDM rat model

Male Wistar neonatal rats at age 1.5 days (Streptozotocin [STZ] group 1) and 5 days (STZ group 2) received a subcutaneous injection of 90 mg/kg STZ. After 10 weeks, the rats were subjected to an oral glucose tolerance test (OGTT) (2 g/kg) in a conscious state. The pancreas perfusion experiments were conducted 2 weeks after the OGTT. There was no statistical difference in insulin response between the STZ group 1 and the control group. On the contrary, in the STZ group 2, the plasma glucose response to OGTT showed a typical diabetic pattern, and the plasma insulin response was markedly blunted. In the isolated perfused rat pancreas, the infusion of glucose evoked a biphasic insulin secretion, but the peak insulin levels induced by 16.7 mmol/L glucose in the STZ group 1 were significantly lower than in the controls. We further investigated characteristics of insulin secretion in response to different secretagogues in these animal models using isolated islets. The insulin content of the islets of the STZ group 1 were about one half that of the control group. Insulin secretion in the STZ group 1 was impaired in response to glucose stimulation, but remained normal in response to arginine and forskolin. These results suggest that insulin secretion of non-insulin-dependent diabetes mellitus (NIDDM) rat model is selectively impaired in response to glucose stimulation, possibly due to a disorder of signaling mechanism other than adenylate cyclase.     

Changes in islet blood flow in rats with NIDDM

Summary Islet blood flow was quantified in NIDDM rats either of the GK strain on after neonatal injection of STZ (n0-STZ), using the non-radioactive microsphere technique. In the basal state, there was a good correlation between plasma insulin level and islet blood flow, i.e. both were increased or decreased in comparison to those of control rats in GK and n0-STZ rats, respectively. The increased islet blood flow and plasma insulin levels observed in the GK rats were abolished by bilateral subdiaphragmatic vagotomy. During a glucose challenge, whereas plasma insulin and islet blood flow were doubled in control rats, these parameters were not modified in the diabetic rats. These data demonstrate an alteration in the islet blood flow of diabetic rats during a glucose challenge which could participate in the abnormal glucose-induced insulin secretion previously described in these two models.Abbreviations NIDDM non-insulin-dependent diabetes mellitus - STZ streptozotocin     

运动对糖尿病大鼠骨骼肌GLUT4和MAPK的作用

目的 研究适量运动对糖尿病大鼠骨骼肌葡萄糖转运蛋白（GLUT4）和丝裂素活化蛋白激酶（MAPK）活性的作用。方法 40只SD大鼠分为四组：糖尿病非运动组,糖尿病运动组,正常非运动组和正常运动组。运动组进行12周的中等强度的跑步训练。结果 （1）糖尿病大鼠血糖浓度增高,血胰岛素浓度降低;骨骼肌组织葡萄糖转运蛋白（GLUT4）含量下降,肝脏,胰腺和骨股长肌的丝裂素活化蛋白激酶（MAPK）活性下降,（2）糖尿病运动组大鼠经12周跑步训练后,血糖浓度下降,血胰岛素浓度升高;骨骼肌组织的GLUT4含量增加;肝脏,骨骼肌和胰腺的MAPK活性增加。结论 适量运动可增加骨骼肌GLUT4的蛋白含量以及增强肝脏和骨骼肌MAPK的活性,这可能是运动改善糖尿病糖代谢紊乱的机制之一。     

T型和L型钙通道阻断剂改善大鼠糖尿病肾功与糖,脂代谢无关

目的阐明Ｔ通道阻滞剂米贝地尔和Ｌ通道阻滞剂氨氯地平对实验性糖尿病鼠肾的保护作用是否基于改善糖、脂水平。方法雄性ＳＤ大鼠右肾切除,给予链脲佐菌素（ＳＴＺ）按６５ｍｇ／ｋｇ腹腔注射。米贝地尔组（Ｍｉｂ,３０ｍｇ／ｋｇ,ｑｄ,ｎ＝６）;氨氯地平组（Ａｍｌ,...     

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.     

Effects of Gmelina arborea extract on experimentally induced diabetes

ObjectiveTo study the effects of aqueous extract of Gmelina arborea bark on normoglycemic levels and streptozotocin (STZ) induced diabetes in rats.MethodsAfter single administration of the aqueous extract, plasma glucose level was determined up to 6 h. In subacute study, the aqueous extract was administered for 28 d and plasma glucose level was determined weekly. The diabetes was induced in rats by the intraperitoneal injection of STZ at a dose of 55 mg/kg body weight. The diabetic animals were divided into four groups containing six in each: Group I diabetic control, Group II and III treated with the aqueous extract respectively at a dose of 250 and 500 mg/kg body weight once daily and Group IV treated with glibenclamide at a dose of 0.6 mg/kg body weight once daily. In acute study, the aqueous extract and glibenclamide were administered orally to rats. Plasma glucose levels were determined at 30, 60, 120, 240 and 360 min after the administration of the test samples. To study subacute effects, test samples (the aqueous extract and glibenclamide) were administered for 28 d consecutively. The effects of each test sample on plasma glucose level, body weight as well as food and water intake were also monitored weekly. The oral glucose tolerance test and biochemical indicators were estimated on day 28.ResultsThe aqueous extract did not significantly decrease the plasma glucose level in the normoglycemic rats as shown by the acute and subacute assays. However, after oral administration of the aqueous extract, the plasma glucose level was significantly (P<0.001) decreased in the diabetic rats in the acute study. The long-term administration of the aqueous extract significantly (P<0.001) reduced plasma glucose levels of the diabetic rats. Additionally, the aqueous extract also reduced loss of body weight and significantly decreased food and water intake in the diabetic animals. Nevertheless, no effects on biochemical indicators were observed at the selected doses.ConclusionsThe aqueous extract of Gmelina arborea bark had antihyperglycemic activity against STZ induced diabetes in rats, after single and subacute oral administration. Moreover, it did not show significant glucose lowering effect in normoglycemic rats.     

Effect of streptozotocin diabetes and insulin replacement on growth hormone in rats

The effects of insulin deprivation on the growth rate, plasma and pituitary growth hormone (GH) and GH synthesis were investigated in male Wistar rats. Diabetes was induced by administration of streptozotocin (STZ), 7 mg/100 g bw, and plasma and pituitary GH levels were measured by means of a specific radioimmunoassay. GH synthesis was determined in pituitaries by the in vitro incorporation of [3H] leucine into specific immunoprecipitates. The body weight and the pituitary GH content of normally developing rats showed an almost linear increase throughout the observation period, whereas diabetic rats stopped growing immediately after receiving STZ, and remained smaller than age-paired controls. Pituitary GH content remained within the control range through the 5 days following STZ administration and thereafter decreased reaching 10% of control values by the 30th day. Furthermore, pituitaries from diabetic rats incorporated [3H] leucine into r-GH at a greatly reduced rate, which could explain the diminished r-GH storage in pituitaries of diabetic rats. Plasma GH concentrations remained within the normal range for 10 days after STZ, thereafter plasma GH were markedly reduced. Insulin treatment prevented the metabolic changes, and restored normal levels of plasma and pituitary GH in diabetic rats. These findings indicate that diabetes, in rat, is characterized by an inhibitory effect on GH secretion, probably via a diminished GH synthesis by the pituitary gland.