Effect of cogent db,a herbal drug,on plasma insulin and hepatic enzymes of glucose metabolism in experimental diabetes

Aims: The present study was designed to investigate the effect of cogent db, a polyherbal drug on blood glucose, plasma insulin and the activities of hepatic glucose metabolic enzymes in alloxan-induced diabetic rats.
Methods: Male Wistar rats body weight of 180–200 g (six normal and 18 diabetic rats) were used in this study. The rats were divided into four groups after the induction of alloxan diabetes. In the experiment, six rats were used in each group: Group 1, normal rats given 2 ml of saline; Group 2, diabetic control rats given 2 ml of saline; Group 3, diabetic rats given aqueous solution of cogent db (0.45 g/body kg weight); and Group 4, diabetic rats given aqueous solution of glibenclamide (600 µg/kg body weight). The treatment was given for 40 days. After the treatment, fasting blood glucose, plasma insulin, urine sugar and the activities of hepatic glucose metabolic enzymes were determined in normal and experimental animals.
Results: Treatment with cogent db resulted in a significant reduction in blood glucose and the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase in the liver, whereas the level of plasma insulin and hepatic hexokinase activity were significantly increased in alloxan-diabetic rats.
Conclusions: The present investigation suggests that cogent db controls the blood glucose level by increasing glycolysis and decreasing gluconeogenesis with a lower demand of pancreatic insulin than in untreated rats. This is possible because it regulates the activities of hepatic glucose metabolic enzymes.     

Antidiabetic effect of diasulin, a herbal drug, on blood glucose, plasma insulin and hepatic enzymes of glucose metabolism in hyperglycaemic rats

AIM: The present study was designed to investigate the effect of diasulin, a polyherbal drug, on blood glucose, plasma insulin and the activities of hepatic glucose metabolic enzymes in alloxan-induced diabetic rats. METHODS: Male Wistar rats, body weight of 180-200 g (12 normal and 30 diabetic rats), were used in this study. The rats were divided into seven groups after the induction of alloxan diabetes. In the experiment, six rats were used in each group. Group 1: normal rats given 2 ml of saline; group 2: normal rats given aqueous solution of diasulin (0.20 g/kg of body weight); group 3: diabetic control rats given 2 ml of saline; group 4: diabetic rats given aqueous solution of diasulin (0.05 g/kg of body weight); group 5: diabetic rats given aqueous solution of diasulin (0.10 g/kg of body weight); group 6: diabetic rats given aqueous solution of diasulin (0.20 g/kg of body weight) and group 7: diabetic rats given aqueous solution of glibenclamide (600 micro g/kg of body weight). The treatment was given for 30 days. After the treatment, fasting blood glucose, plasma insulin, urine sugar and the activities of hepatic glucose metabolic enzymes were determined in normal and experimental animals. RESULTS: Treatment with diasulin resulted in a significant reduction in blood glucose, glycosylated haemoglobin and an increase in plasma insulin and total haemoglobin and a significant improvement in glucose tolerance. Diasulin also resulted in a significant reduction in the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase in the liver, whereas the level of plasma insulin and hepatic hexokinase activity was significantly increased in alloxan diabetic rats. CONCLUSIONS: The present investigation suggests that diasulin, a polyherbal drug, controls the blood glucose level by increasing glycolysis and decreasing gluconeogenesis with a lower demand of pancreatic insulin than in untreated rats. This is possible, because it regulates the activities of hepatic glucose metabolic enzymes.     

Change in the lipid profile, lipogenic and related enzymes in the livers of experimental diabetic rats: effect of insulin and vanadate

Administration of sodium orthovanadate to diabetic animals exhibits insulin-like effects and has been effective in the reversal of biochemical complications. This study evaluates the effect of sodium orthovanadate (0.6 mg/ml) treatment for 21 days on the hepatic glucose homeostasis and lipid metabolism in alloxan diabetic rats. The activities of two lipogenic enzymes, glucose-6-phosphate dehydrogenase and malic enzyme; and related enzymes, hexokinase and glucose-6-phosphatase were measured in the liver cytosolic fractions of diabetic rats and diabetic rats treated separately with insulin and sodium orthovanadate. The total lipids, triglycerides and cholesterol levels were estimated in the livers of the diabetic and the treated rats. The activities of both the lipogenic enzymes and hexokinase isozymes were significantly decreased, whereas the activity of glucose-6-phosphatase was significantly increased in the diabetic liver. During diabetes, the levels of total lipids and triglycerides increased significantly with a decrease in the cholesterol levels in the liver. Insulin and vanadate were able to restore the altered enzyme activities to almost control levels. Both insulin and vanadate were found to partially restore the altered levels of total lipids, triglycerides and cholesterol in the livers of diabetic rats. The results indicate that vanadate administration to diabetic animals normalizes blood glucose and causes marked improvement of altered lipid metabolism during diabetes. The present study and earlier reports suggest the possible use of vanadate as insulin replacement in the therapy of diabetes when administered at pharmacological doses.     

Antidiabetic, hypolipidemic and histopathological analysis of Dillenia indica (L.) leaves extract on alloxan induced diabetic rats

ObjectiveTo investigate antidiabetic, hypolipidemic histopathological analysis of Dillenia indica (D. indica) methanolic leaves (DIME) extract in alloxan induced diabetic rat by administering oral doses (250 and 500 mg/kg body weight).MethodsBlood glucose levels were measured using blood glucose test strips with elegance glucometer on weekly intervals till the end of study (i.e. 3 weeks). Other parameters e.g. liver profile, renal profile and total lipid levels were determined in normal and alloxan induced diabetic rats after oral administration of the extract for 21 days. Histopathological changes in diabetic rat organs (pancreas, liver and kidney) were also observed after extract treatment.ResultsDaily oral administration DIME (250 and 500 mg/kg body weight) and glibenclamide (10 mg/kg) showed beneficial effects on blood glucose level (P < 0.001) as well as improving kidney, liver functions and hyperlipidaemia due to diabetes. The extract treatment also showed to enhanced serum insulin level and body weight of diabetic rats as compared to diabetic control group. Furthermore, the extract has a favorable effect on the histopathological changes of the pancreas, liver and kidney in alloxan induced diabetes.ConclusionsD. indica possess antidiabetic property as well improve body weight, liver profile, renal profile and total lipid levels. DIME has also favorable effect to inhibit the histopathological changes of the pancreas and kidney in alloxan induced diabetes.     

Effects of probucol on hepatic tumor necrosis factor-α, interleukin-6 and adiponectin receptor-2 expression in diabetic rats

Background and Aims:  Probucol is a lipid-lowering agent with anti-oxidant effects. Oxidative stress and inflammation are important in the pathophysiology of insulin resistance. We aimed to evaluate the effects of probucol on liver histological changes, serum and hepatic levels of adipokines in rats with high fat-induced type 2 diabetes (T2D).
Methods:  Thirty-six rats were divided into a normal control group, a high fat-induced T2D group and a probucol treatment group. After six weeks of treatment with probucol, we evaluated liver histological changes and measured homeostasis model assessment index (HOMA-IR), serum superoxide dismutase (SOD), alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor (TNF)-α, interleukin (IL)-6, adiponectin and hepatic TNF-α, IL-6 and adiponectin receptor-2 (adipoR2) mRNA.
Results:  The degree of hepatic steatosis and inflammation, HOMA-IR, serum ALT, TNF-α and IL-6 concentrations, and hepatic TNF-α and IL-6 mRNA expression in diabetic rats were significantly higher compared with normal controls. Serum SOD and adiponectin concentrations and hepatic adipoR2 mRNA expression in diabetic rats were significantly lower compared with normal controls. Probucol significantly reduced the degree of hepatic steatosis, HOMA-IR, serum ALT, TNF-α and IL-6 concentrations, and hepatic TNF-α and IL-6 mRNA expression. Probucol significantly raised serum SOD and adiponectin concentrations and hepatic adipoR2 mRNA expression.
Conclusions:  In rats with high fat-induced T2D, treatment with probucol improved insulin sensitivity, hepatic steatosis by raising circulating adiponectin and hepatic adipoR2 levels, in addition to reducing pro-inflammatory cytokines in the circulation and liver.     

Effects of cortisol and progesterone on insulin binding and lipogenesis in adipocytes from normal and diabetic rats

Cortisol implants in normal and diabetic rats reduced body weight, adiposity, insulin receptor concentration and both basal and insulin-stimulated rates of lipogenesis in isolated adipocytes, whilst insulin sensitivity was unchanged. In normal but not diabetic rats these changes were accompanied by increased serum glucose and insulin concentrations. In contrast, progesterone implants in normal and diabetic rats increased body weight gain, adiposity, insulin receptor concentration and both basal and insulin-stimulated rates of lipogenesis in adipose tissue, again without affecting insulin sensitivity. Progesterone did not affect serum insulin concentrations in normal or diabetic rats but accelerated the decline in serum glucose concentrations which occurred during an overnight fast in diabetic rats. The results suggest that cortisol inhibits lipogenesis in adipose tissue without affecting insulin sensitivity, cortisol reduces insulin binding in adipose tissue without a requirement for hyperinsulinaemia, which might itself indirectly lead to down-regulation of the insulin receptor, and in diabetic rats progesterone stimulates lipogenesis in adipose tissue without any increase in food intake or serum insulin concentrations suggesting that progesterone may have a direct anabolic role in adipose tissue.     

Ciliary neurotrophic factor improves diabetic parameters and hepatic steatosis and increases basal metabolic rate in db/db mice

Obesity plays a central role in the development of insulin resistance and type 2 diabetes. We therefore examined the effects of a modified form of ciliary neurotrophic factor [Axokine, which is hereafter referred to as ciliary neurotrophic factor (CNTF)Ax15], which uses a leptin-like mechanism to reduce body weight, in the db/db murine model of type 2 diabetes. In previous studies, weight loss produced by CNTF treatment could largely be attributed to its effects on food intake. In contrast, CNTFAx15 treatment of db/db mice caused significantly greater weight loss and marked improvements in diabetic parameters (e.g., levels of glucose, insulin, triglyceride, cholesterol, and nonesterified free fatty acids) than could be accounted for by reduced caloric intake alone. These beneficial effects, above and beyond those seen in animals controlled for either food restriction or body weight, correlated with the ability of CNTFAx15 to increase metabolic rate and energy expenditure and reduce hepatic steatosis while enhancing hepatic responsiveness to insulin. The hepatic effects were linked to rapid alterations in hepatic gene expression, most notably reduced expression of stearoyl-CoA desaturase 1, a rate-limiting enzyme in the synthesis of complex lipids that is also markedly suppressed by leptin in ob/ob mice. These observations further link the mechanisms of CNTF and leptin action, and they suggest important, beneficial effects for CNTF in diabetes that may be distinct from its ability to decrease food intake; instead, these effects may be more related to its influence on energy expenditure and hepatic gene expression.     

Antidiabetic activity of the mangrove species Ceriops decandra in alloxan-induced diabetic rats

Background: Diabetes is a series of disorders characterized by increased fasting and postprandial glucose concentration and insulin deficiency and/or decreased insulin action. Although there are a number of commercially available drugs for the treatment of diabetes, their long‐term use may cause unwanted side effects. Consequently, many studies are underway to find natural remedies that can effectively reduce the intensity of diabetes. The aim of the present study was to evaluate the antidiabetic activity of the mangrove species Ceriops decandra. Methods: The effects of daily oral administration of an ethanolic extract from the leaves of C. decandra (30, 60, 120 mg/kg) for 30 days on blood glucose, hemoglobin (Hb), HbA1c, liver glycogen and some carbohydrate metabolic enzymes were evaluated in normal and alloxan‐induced diabetic rats. The effects of these extracts were compared with the effect of 30‐days treatment with 0.1 mg/kg, p.o., glibenclamide, a commercially available drug commonly used in the treatment of diabetes. Results: Oral administration of 120 mg/kg extract modulated all the parameters evaluated to levels seen in control rats. The effects of 120 mg/kg extract were comparable to those of glibenclamide. Conclusion: The extract of the mangrove plant C. decandra exhibited promising antidiabetic activity and could be considered for further evaluation in clinical studies and drug development.     

The effect of long-term glibenclamide treatment on glucose tolerance, insulin secretion and serum lipids in subjects with impaired glucose tolerance

The effects of glibenclamide plus diet (n = 27) or diet alone (n = 18) on glucose tolerance, insulin secretion and serum lipids in non-obese subjects with normal or low insulin responses and impaired glucose tolerance (IGT) has been followed up for two years. Glucose tolerance and insulin secretion were characterized by means of a glucose infusion test consisting of an initial injection of 0.33 g glucose/kg body weight followed by 12 mg/kg body weight/min for 2 h. Dietary treatment did not improve glucose tolerance in normal and low insulin-responders. Glibenclamide plus diet succeeded in improving glucose tolerance only in low insulin responders whereas glucose tolerance remained unchanged in normal insulin responders. There was a significant decrease in fasting and glucose-stimulated insulin levels after two years of glibenclamide treatment in both the normal and low insulin-responders. The body weight was not altered. Triglyceride and cholesterol levels both decreased. In summary, the present study failed to demonstrate an increase in insulin secretion under chronic administration of glibenclamide in subjects with IGT independent of the type of insulin response. From the practical point of view, glibenclamide is of benefit in the treatment of non-obese subjects with IGT and relative insulin deficiency.     

Insulin mimetic effects of macrocyclic binuclear oxovanadium complexes on streptozotocin-induced experimental diabetes in rats

Aim:  The vanadium complexes so far tested for their insulin mimetic effects are either mono- or binuclear and contain only acyclic ligands. The leaching or hydrolysis of vanadyl ions from these complexes is much easier, and hence they elicit side effects. In the present study, a new binuclear macrocyclic oxovanadium complex was synthesized, and its efficacy was studied on streptozotocin (STZ)-induced diabetic rats over a period of 30 days.
Methods:  The insulin mimetic effect of the complex was tested on the blood sugar level in the STZ-diabetic rats and on the activities of the carbohydrate-metabolizing enzymes present in the liver.
Results:  Administration of vanadium complex to STZ-induced diabetic rats decreased blood glucose levels from hyperglycaemic to normoglycaemic when compared to diabetic rats. The activity of carbohydrate-metabolizing enzymes such as hexokinase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen content were increased to near normal in vanadium complex-administered diabetic rats. The biochemical studies such as assay of blood urea and glutamate oxaloacetate transaminases revealed that the complex is not toxic to the system.
Conclusion:  The nontoxic nature of this complex may be due to the presence of the vanadyl ions in an intact macrocyclic form. Further, the vanadyl ions present in the macrocyclic binuclear oxovanadium complex are very close to each other, and this may enhance the insulin mimetic activity by synergic effect.     

Influence of treatment with acarbose or glibenclamide on insulin sensitivity in type 2 diabetic patients

Aim: The aim of our double-blind, placebo-controlled study was to compare the effect of acarbose and glibenclamide on the insulin sensitivity in type 2 diabetes.
Methods: We investigated 77 patients (mean age 58.7 years, mean BMI 27.3 kg/m²), treated by diet alone for at least 4 weeks. The subjects were randomized into three treatment groups for 16 weeks: 100 mg t.i.d. acarbose ( n  = 25) or 1 mg t.i.d. glibenclamide ( n  = 27) or one t.i.d. placebo ( n  = 25). Before and after therapy, the levels of fasting plasma glucose, glycosylated haemoglobin, fasting insulin, plasma glucose and insulin 1 h after a standardized breakfast were measured and insulin sensitivity determined by euglycaemic hyperinsulinaemic clamp test.
Results: After the treatment period, BMI in the acarbose and placebo group decreased significantly, whereas in the glibenclamide group a significant increase was observed. Fasting plasma glucose was only significant reduced under glibenclamide. The postprandial glucose decreased significantly after acarbose (13.8 vs. 11.4 mmol/l, p < 0.05) and glibenclamide treatment (14.6 vs. 11.4 mmol/l, p < 0.05) and was unchanged under placebo (13.8 vs. 13.7 mmol/l). The fasting insulin levels remained unchanged in all three groups, whereas postprandial insulin values increased significantly under glibenclamide. Neither acarbose nor glibenclamide significantly changed insulin sensitivity [acarbose: glucose disposal rate before treatment 2.3 mg/kg body weight/min/insulin, after treatment 3.2; glibenclamide 2.2 vs. 2.1; placebo 2.6 vs. 3.0].
Conclusions: Our results show a more substantial improvement of glucose control under glibenclamide than under acarbose which, however, was not associated with an increase of insulin sensitivity.     

Associates of change in liver fat content in the morbidly obese after laparoscopic gastric banding surgery

Aim:  Hepatic steatosis affects up to 30% of the population. After weight loss, monitoring of the change in hepatic steatosis is not routinely performed. This study aimed to define the closest associates of change in liver fat content in a population of obese females following laparoscopic gastric banding surgery.
Methods:  Before and 3 months after surgery, proton magnetic resonance spectroscopy and magnetic resonance imaging were used to estimate the amount of lipid contained within the liver and abdominal subcutaneous and visceral compartments of 29 obese [mean body mass index (BMI) 39 ± 5 kg/m²], non-diabetic women aged between 20 and 62 years. Liver enzymes, fasting plasma glucose and insulin were also measured as well as body weight, BMI and waist circumference. Insulin sensitivity was estimated using homeostasis model assessment insulin resistance index.
Results:  Significant reductions occurred in body weight (p < 0.001), abdominal fat volumes (p < 0.001) and liver fat (p = 0.037) 3 months after surgery. Change in liver fat content more closely associated with change in serum gamma-glutamyl transferase (GGT; r = 0.71, p < 0.001) than with changes in weight (r = 0.10, p = 0.612) and waist circumference (r = 0.15, p = 0.468).
Conclusions:  Our findings suggest that obese non-diabetic female patients who have undergone significant weight loss over 3 months can be better assessed for the regression of excess liver fat content by monitoring changes in serum GGT levels rather than changes in simple anthropometry.     

Phytopharmacological evaluation of Byesukar for hypoglycaemic activity and its effect on lipid profile and hepatic enzymes of glucose metabolism in diabetic rats: Original Article

Many anti-diabetic herbal preparations have been recommended in alternative systems of medicine for the treatment of diabetes. No systematic study has been done on the anti-diabetic efficacy of Byesukar, a polyherbal formulation to treat diabetes. The anti-diabetic efficacy of byesukar ethanol extract was evaluated in an animal model of diabetes induced by alloxan. Male Wistar rats were divided in to four groups. Group 1 was normal control group; group 2 and 3 received alloxan. After inducing experimental diabetes group 2 served as diabetic control; group 3 received byesukar (500 mg/kg body weight) orally for 30 consecutive days. Group 4 were normal rats which received byesukar extract alone. The effect of byesukar on glucose level in diabetic rats was studied and the level of glucose metabolizing enzymes (Hexokinase, glucose-6-phosphatase and fructose 1, 6-bisphosphatase) in the liver and kidney were estimated. The effect of byesukar on the serum and tissue lipid profile (Cholesterol, triglycerides, phospholipids and free fatty acids) were also estimated in diabetic rats. Our results indicate that treatment with byesukar resulted in significant reduction of blood glucose, tissue glucose-6-phosphatase and fructose 1, 6-bisphosphatase activity. The decreased tissue hexokinase activity in diabetes state was found to be significantly increased by byesukar treatment. Also the byesukar treated diabetic rats showed a significant decrease in the tissue lipid profile compared to the diabetic rats. In conclusion the decreased blood glucose accompanied with decreased lipid profile and changes in the activities of the glucose metabolizing enzymes shows the antidiabetic effect of byesukar.     

Long-term and rapid regulation of ob mRNA levels in adipose tissue from normal (Sprague Dawley rats) and obese [db/db mice,fa/fa rats) rodents

Summary Increased levels of mRNA transcribed from the ob gene in adipose tissue of obese/hyperinsulinaemic Zucker (fa/fa) rats were detectable as early as 3 weeks after birth and continued to rise there after in parallel with body weight and serum insulin. mRNA levels of two other fat-specific genes (ARL4, FST44) were unaltered. In C57BL/KsJ db/db mice, ob mRNA levels also increased in parallel with body weight and serum insulin, and remained elevated in older animals when insulin levels decreased. In heterozygous control animals (db/ + ; fa/Fa), mRNA levels were comparable with those in the homozygous controls. In normal Sprague Dawley rats, the ob mRNA increased continuously, but more slowly than in Zucker rats, in parallel with body weight and insulin levels, and reached 15 times higher levels in the heaviest rats (400 g) studied. In Sprague Dawley rats made diabetic by an injection of streptozotocin, ob mRNA levels were reduced by approximately 50 % after 24 h. A 24-h fasting period reduced the ob mRNA by 50 % in lean Sprague Dawley and Fa/Fa, but not in obese Zucker fa/fa rats, although insulin levels were reduced in both groups. These data indicate that ob mRNA levels increase in both normal and obese rodents in parallel with age, body weight and serum insulin, reflecting an early (Zucker rats, db-mice) or slowly developing (Sprague Dawley rats) resistance to leptin and insulin. This increase does not appear to be mediated by the recently described rapid regulation of ob mRNA by insulin, but seems to be due to a different, long-term control mechanism which signals the size of the fat depots. [Diabetologia (1996) 39: 758–765] Received: 27 October 1995 and in revised form: 5 December 1995     

Tissue-specific correction of lipogenic enzyme gene expression in diabetic rats given vanadate

Summary Vanadium is a potent insulinomimetic agent. In vivo, its blood glucose lowering action in insulin-deficient diabetic rats is associated with corrected expression of genes involved in hepatic glucose metabolism. In this study, we investigated whether vanadate treatment also reverses the impaired expression of genes coding for key enzymes of lipogenesis in diabetic liver and white adipose tissue. Oral administration of vanadate to streptozotocin-rats caused a 55% fall in plasma glucose levels after feeding without modifying low insulinaemia. It also partially corrected the low thyroid hormone concentrations. In untreated diabetic animals, hepatic mRNA levels of acetyl-CoA carboxylase and fatty acid synthase were reduced by more than 80 and 90%, respectively, in close correlation with changes in enzyme activities. Three weeks of vanadate treatment totally restored acetyl-CoA carboxylase mRNA and partially restored fatty acid synthase mRNA (71% of control levels). The activities of both lipogenic enzymes were increased 3.5 to 4-fold, to reach 45 to 65% of control values. By contrast, in white adipose tissue, vanadate modified neither expression nor activity of both lipogenic enzymes, which remained blunted (<10% of control levels). In conclusion, vanadate treatment partially restores the activities of two key lipogenic enzymes in liver, but not in white adipose tissue, of diabetic rats. This correction results from a reversal of impaired pre-translational regulatory mechanisms possibly mediated by an improvement of thyroid function and a selective restoration of liver glycolytic flux.Abbreviations ACC Acetyl-CoA carboxylase - FAS fatty acid synthase - PEPCK phosphoenolpyruvate carboxykinase - C non-diabetic control rats - D untreated diabetic rats - V vanadate-treated diabetic rats - SSC sodium saline citrate - SDS sodium dodecyl sulphate - OD optical density - kb kilobase     

Circulating and liver tissue levels of retinol-binding protein-4 in non-alcoholic fatty liver disease

Aim:  Retinol-binding protein-4 (RBP4) has been proposed as a new adipokine that regulates insulin action in muscles and the liver, and contributes to the pathogenesis of insulin resistance. As non-alcoholic fatty liver disease (NAFLD) is related to insulin resistance, we aimed to evaluate RBP4 levels in the serum and liver of patients with NAFLD.
Methods:  Serum RBP4 was measured in 30 NAFLD patients and 30 matched healthy controls. RBP4 expression in the liver of NAFLD patients was shown by immunohistochemistry.
Results:  Serum RPB4 was significantly lower in NAFLD patients compared with controls (25.15 vs 34.66 µg/mL, P  < 0.001) and there was no correlation with metabolic parameters or insulin resistance. RBP4 liver tissue immunostaining was more extensive and intense in NAFLD liver compared with normal liver and the RBP4 immunohistochemical score was positively correlated with the grade of steatosis, grade of non-alcoholic steatohepatitis activity and stage of fibrosis.
Conclusions:  In NAFLD patients, serum RBP4 was significantly lower as compared with controls and did not correlate with insulin resistance. In contrast, RBP4 liver tissue expression was enhanced and correlated with NAFLD histology.     

Less frequent body weight gain in elderly type 2 diabetic patients treated with glimepiride

Background:   The purpose of the present paper was to study the effect of a new sulfonylurea, glimepiride, which has an extra-pancreatic action that improves insulin resistance, on glycemic control and body weight gain in elderly patients with type 2 diabetes mellitus (DM).
Methods:   Thirty-seven type 2 diabetic patients being treated with either gliclazide or glibenclamide were switched to glimepiride for 6 months and clinical parameters were compared between elderly (≥ 65 years old, n  = 9) and non-elderly (< 65 years old, n  = 28) patients.
Results:   There was no significant difference between the two groups in baseline characteristics, or in changes in fasting plasma glucose (FPG) and HbA1c. For body weight change, however, none of the elderly patients (0/9) exhibited an increase, but 9 of 28 (32%) non-elderly subjects showed body weight gain ( P  < 0.05).
Conclusions:   Body weight gain with glimepiride treatment is less frequent in elderly patients with type 2 DM than in non-elderly patients with the disease. These data together with the recent increase in obese elderly patients with diabetes suggest that glimepiride is recommended for treatment of type 2 diabetes in this age group.     

PEGylation improves the hypoglycaemic efficacy of intranasally administered glucagon-like peptide-1 in type 2 diabetic db/db mice

Aims:  PEGylation – covalent modification of therapeutic peptides with polyethylene glycol (PEG) – is viewed as an effective way of prolonging the short lifetime of glucagon-like peptide-1 (GLP-1). In this study, we investigated the hypoglycaemic efficacies of PEGylated GLP-1s administered intranasally in type 2 diabetic db / db mice.
Methods:  Three types of site-specific (Lys³⁴) PEGylated GLP-1 analogues (PEG molecular weight: 1, 2 or 5 kDa) were synthesized. Their metabolic stabilities were evaluated in nasal mucosa enzyme pools. Oral glucose tolerance test was conducted 30, 60 and 120 min after intranasally administering these analogues in type 2 diabetic db / db mice.
Results:  PEGylated GLP-1 analogues were found to have significantly longer half-lives than native GLP-1 in nasal mucosa enzymes (2.4-fold to 11.0-fold, p < 0.005). Non-PEGylated GLP-1 at 100 nmol/kg was not found to have marked efficacy irrespective of nasal administration time [total hypoglycaemic degree (HD_total) values 2.8–17.3%]. On the contrary, PEGylated GLP-1s (100 nmol/kg) showed obvious efficacies with maximum HD_total values of >51.8 ± 5.8% (p < 0.005 vs. GLP-1).
Conclusion:  This study highlights the pharmacological potential of intranasally administered PEGylated GLP-1s in terms of stabilizing postprandial hyperglycaemia in type 2 diabetic patients.     

Comparison of the antidiabetic effects of brain-derived neurotrophic factor and thiazolidinediones in obese diabetic mice

AIMS: Brain-derived neurotrophic factor (BDNF) ameliorates glucose metabolism in obese diabetic db/db mice. The antidiabetic effect of BDNF is dependent on plasma insulin levels, and BDNF enhances insulin action by modulating insulin signalling in peripheral tissues. The aim of the study was to compare the antidiabetic effects of BDNF with those of thiazolidinediones (TZDs), which are insulin-sensitizing agents, through evaluation of the effects of BDNF and TZDs on glucose metabolism, energy expenditure, pancreatic function and hepatic steatosis in db/db mice. METHODS: The effects of BDNF, pioglitazone and rosiglitazone on blood glucose concentration, body weight and pancreatic insulin and glucagon contents and the effects of BDNF and troglitazone treatment for 3 weeks on blood glucose concentration, body and liver weights and histological liver images were examined in db/db mice. Furthermore, since BDNF reduces food intake in obese hyperphagic diabetic mice, the effects of BDNF treatment for 3 weeks on blood glucose concentration, body weight, fat pad and liver weights and rectal temparature in db/db mice were compared with those of troglitazone under pair-fed conditions. RESULTS: BDNF, pioglitazone and rosiglitazone all ameliorated hyperglycaemia in db/db mice, but BDNF increased the pancreatic insulin content more effectively than pioglitazone and rosiglitazone. The pancreatic glucagon content decreased with BDNF, but increased with pioglitazone and rosiglitazone compared with vehicle, and body weight and liver weight increased with troglitazone, but decreased with BDNF compared with vehicle. Histological analysis of the liver showed that BDNF treatment reduced the massive vacuolization observed with vehicle, whereas troglitazone worsened the vacuolization. Body weight, fat pad and liver weights in BDNF-treated mice were significantly lower than those in pair-fed troglitazone-treated db/db mice, and rectal temperature in BDNF-treated mice was significantly higher than that in pair-fed troglitazone-treated mice, suggesting that BDNF enhances energy expenditure. CONCLUSIONS: These data suggest that compared with TZDs, BDNF potently ameliorates pancreatic dysfunction, fatty liver and energy expenditure, thereby exerting favourable antidiabetic effects in type 2 diabetic mice.     

Antidiabetic effects of sage (Salvia officinalis L.) leaves in normal and streptozotocin-induced diabetic rats

BackgroundSage (Salvia officinalis L.) has a wide range of biological activities, such as anti-oxidative properties, anti-bacterial, hypoglycemic, anti-inflammatory, fungistatic, virustatic, astringent, eupeptic and anti-hydrotic effects. This study was designed to examine the antidiabetic effect of sage ethanolic extract in normal and streptozotocin-induced diabetic rats.MethodsOral administration of sage extract (0.1, 0.2, and 0.4 g/kg body weight) and glibenclamide (600 μg/kg) for 14 days on the level of serum glucose, triglycerides, total cholesterol, urea, uric acid, creatinine, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in normal and streptozotocin-induced diabetic rats were evaluated.ResultsOral administration of 0.2 and 0.4 g/kg body wt. of the sage extract for 14 days exhibited a significant reduction in serum glucose, triglycerides, total cholesterol, urea, uric acid, creatinine, AST, ALT and increased plasma insulin in streptozotocin-induced diabetic rats but not in normal rats. Glibenclamide was used as reference and showed similar antidiabetic effect.ConclusionsIt is concluded that the traditional use of S. officinalis as an antidiabetic agent is justified and that extracts from this plant show a dose-dependent activity which is comparable to the standard antidiabetic drug glibenclamide.