The relation of the glycated serum protein, fructosamine, to serum protein, albumin, and glucose concentrations was examined in healthy dogs, dogs with hypo- or hyperproteinemia, and diabetic dogs. Fructosamine was determined by use of an adaptation of an automated kit method. The reference range for fructosamine in a composite group of control dogs was found to be 1.7 to 3.38 mmol/L (mean +/- SD, 2.54 +/- 0.42 mmol/L). Fructosamine was not correlated to serum total protein, but was highly correlated to albumin in dogs with hypoalbuminemia. To normalize the data with respect to albumin, it is suggested that the lower limit of the reference range for albumin concentration (2.5 g/dl) be used for adjustment of fructosamine concentration and only in hypoalbuminemic dogs. In 6 hyperglycemic diabetic dogs, fructosamine concentration was well above the reference range. It is concluded that although fructosamine may be a potentially useful guide to assess the average blood glucose concentration over the preceding few days in dogs, further study is required to establish its value as a guide to glucose control in diabetic dogs.

Although benfotiamine has various beneficial anti-diabetic effects, the detailed mechanisms underlying the impact of this compound on the insulin signaling pathway are still unclear. In the present study, we evaluated the effects of benfotiamine on the hepatic insulin signaling pathway in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which are a type 2 diabetes mellitus model. OLETF rats treated with benfotiamine showed decreased body weight gain and reduced adipose tissue weight. In addition, blood glucose levels were lower in OLETF rats treated with benfotiamine. Following treatment with benfotiamine, the levels of Akt phosphorylation (S473/T308) in the OLETF groups increased significantly compared to the OLETF control group so that they were almost identical to the levels observed in the control group. Moreover, benfotiamine restored the phosphorylation levels of both glycogen synthase kinase (GSK)-3¥�/¥�(S21, S9) and glycogen synthase (GS; S641) in OLETF rats to nearly the same levels observed in the control group. Overall, these results suggest that benfotiamine can potentially attenuate type 2 diabetes mellitus in OLETF rats by restoring insulin sensitivity through upregulation of Akt phosphorylation and activation of two downstream signaling molecules, GSK-3¥�/¥� and GS, thereby reducing blood glucose levels through glycogen synthesis.

Carnosine is a dipeptide (β-alanyl-L-histidine) found in mammalian brain, eye, olfactory bulb and skeletal muscle at high concentrations. Its biological functions include antioxidant and anti-glycation activities. The objectives of this study were to investigate anti-diabetic effects of carnosine as determined by blood glucose levels, glucose tolerance test (GTT), glycosylated emoglobin, and serum biochemical and lipid levels in streptozotocin-induced diabetic mice. There were five experimental groups including normal (ICR mice), control (saline), and three groups of carnosine at doses of 6, 30, and 150 mg/kg b.w.. Carnosine was orally administered to the diabetic mice everyday for 12 weeks. There was no significant difference in body weight changes in carnosine-treated groups compared to the control. The treatments of carnosine at the dose of 6 mg/kg significantly decreased the blood glucose level compared with the control at 2 and 4 weeks. The treatments of carnosine at the doses of 6 and 30 mg/kg significantly decreased the blood glucose levels in GTT and glycosylated hemoglobin compared with the control. Carnosine significantly increased total proteins compared with the control. Carnosine at the dose of 6 mg/kg significantly decreased total cholesterol and triglyceride in the serum compared to the control. These results suggest that carnosine at a low level has a hypoglycermic effect resulting from reduction of blood glucose and that a carnosine-containing diet or drug may give a benefit for controlling diabetes mellitus in humans.

A miniature schnauzer (8 years old, male castrated), diagnosed as diabetes mellitus 6 months ahead, were referred to the Veterinary Medical Teaching Hospital of our University with hindlimb stiffness, facial rubbing and tetany. Serum chemistry showed severe hypocalcemia, hypomagnesemia, and measured iPTH (intact pharathyroid hormone) concentration was low (less than 3.0 pmol/L). Consistent rate injection of calcium gluconate (282 mg/kg over 30 min) resulted in prompt relief of the tetany. Then typical treatment for hypoparathyroidism (calcium gluconate and dihydrotachysterol per os) with magnesium administration could control the neuromuscular signs. Diabetes mellitus is being controlled by insulin therapy and prescription diet. Hypomagnesemia in diabetic dog may be induced hypoparathyrodism.

Interactive effect of ethanolic extract of Coccinia indica leaves with glibenclamide (oral hypoglycemic agent) on hypoglycaemic, hypolipidemic and antioxidant effect in alloxan induced diabetic rats was studied. The diabetic rats were administered with C. indica leaf extract at the dose of 100, 150 and 200 mg/kg body weight in combination with glibenclamide at the rate of 0.125 mg/kg. Blood glucose, serum cholesterol and triglyceride were estimated at 15 days intervals and liver glycogen, reduced glutathione and lipid peroxides in tissues at the end of the experiment. All the treatment groups showed significant lowering of blood glucose after 45 days of treatment when compared to the diabetic control. Serum cholesterol and triglycerides also returned to normal levels after 45 days of treatment. Reduced glutathione and lipid peroxide levels were also comparable with that of normal control at the end of the treatment. None of the treatment group showed any severe hypoglycaemia or other toxic effects and the combination of C. indica at the rate of 200 mg/kg with glibenclamide produced the most significant antidiabetic effect. The results suggested that interaction of C. indica with glibenclamide can produce significant hypoglycaemic, hypolipidemic and antioxidant effect in diabetic rats and can be used safely in the treatment of diabetes.

To characterize the roles of C-peptide in vascular homeostatic processes, we examined the genes regulated by C-peptide in LEII mouse lung microvascular endothelial cells. Treatment of the cells with C-peptide increased the expression of c-Jun N-terminal kinase 1 (JNK1) mRNA dose-dependently, accompanied by an increase in JNK1 protein content. Prior treatment of the cells with PD98059, an ERK kinase inhibitor or SB203580, a p38MAPK inhibitor, abrogated the C-peptide-elicited JNK1 mRNA expression. These results indicate that C-peptide increases JNK1 protein levels, possibly through ERK- and p38MAPK-dependent activation of JNK gene transcription.

The aim of this study was to clarify the role of the renal renin-angiotensin system (RAS) in diabetic nephropathy (DN) , which was induced by injection of streptozotocin (STZ). Male CBA/N and CBA/J mice were compared in this study. The former possesses a single renin gene, Ren1. whereas the latter carries two renin genes, Ren1 and Ren2. To examine the molecular dynamics of renal RAS, including renin, angiotensinogen (Agt), angiotensin-converting enzyme (Ace), angiotensin type 1 (Agtr1) and type 2 (Agtr2) receptors in experimental DN, we performed laser-microdissection (LMD) followed by reverse transcriptase nested polymerase chain reaction using each specific primer pairs and immunohistochemistry for renin and angiotensin 2. CBA/N mice had a higher response after injection of STZ than CBA/J mice, showing a significant increase of the kidney/body weight ratio, although there was no significant difference between the two strains for the blood glucose level or pancreatic beta-cell response. The onset of renal pathological changes associated with DN was earlier and more severe in CBA/N mice than in CBA/J mice. Distinct immunoreactivities for renin and angiotensin 2 were newly distributed on the flattered epithelial cells in the dilated distal tubules in the cortex as well as the collecting ducts in the cortex and medulla, and were demonstrated more intensity in CBA/N mice than in CBA/J mice. Micro dissectional analysis in both models revealed a higher incidence of RAS-related gene expression in CBA/J, Ren 2 mice than in CBA-N, Ren 1 mice.

This experiment was carried out to investigate the influence of Aloe vera in the pancreatic islets of streptozotocin diabetic mice. Experimental diabetes was induced in ICR mice with a single injection of SZ (140mg/Kg body weight, ip). The mice demonstrating hyperglycemia 48 hours after SZ injection were treated for 16 days with Aloe vera (300, 800mg/Kg). Plasma glucose was measured, and for morphological studies of the islets specimens were staind with hematoxylin-eosin and by immunocytochemical methods. Then we observed the morphological changes of islets. Polymorphonuclear cells were infiltrated at the periphery of the islets 48 hours after SZ injection in SZ-treated ICR mice, but no prominent WBC infiltration was observed throughout the experiment. Blood glucose in mice treated with Aloe vera after SZ injection was higher than that of SZ injected mice, and mononuclear cells were heavily infiltrated at the islets 16 days after Aloe vera treatment (300mg/Kg), and significant islets infiltration of mononuclear cells was observed 30 days after Aloe vera treatment (800mg/Kg). Islets of ICR mice treated with Aloe vera after SZ injection showed severer insulitis, degranulation and necrosis of B cells than those of SZ injected mice. These studies indicate that Aloe in SZ injected mice increases vascular permeability and number of WBC in pancreatic islets, and potentiates destruction of B cells by cell-mediated immune system