AGE-RELATED MORPHO-FUNCTIONAL CHANGES IN RATS’ PANCREAS UNDER HIGH-FAT DIET-INDUCED INSULIN RESISTANCE AND ITS PHARMACOLOGICAL TREATMENT

The aim: To determine the set of structural and functional changes in pancreatic islets (PI) of obesity-induced insulin resistant (IR) rats of different age (young and old) fed with prolonged (6 month) high-fat diet (HFD) (58% of fat) and further treatment with N-Stearoylethanolamine (NSE), a bioactive N-Acylethanolamine. Materials and methods: Alimentary obesity-induced IR model in rats of two age groups was used to investigate the influence of age and NSE treatment on pancreas morphology (using histological, histochemical and immunohistochemical techniques) and on several biochemical parameters associated with DM onset. Results: The NSE administration normalized pancreas morphology which was more affected in the old IR group; the signs of inflammation, edema, fibrosis and steatosis were somehow diminished and PI area became significantly increased. The amount of the A-F-positive insulocytes increased and TUNEL-positive – decreased. Compensatory hyperplasia in the affected pancreas of both age was an important indicator of NSE stimulating effect. Conclusions: Protective effects of NSE on morpho-functional state of pancreas in HFD-induced IR rats of both age are associated not only with its anti-inflammatory, anti-oxidant and anti-dyslipidemic properties but also with activation of PI hyperplasia and β-cells compensatory mechanisms.

The V369M Gcgr knock-in mice are a precision medicine model of mild Mahvash disease

The detailed metabolic characterization of the glucagon receptor (Gcgr)V369M+/+ mutant mice described in Lin et al. in the Biochemical Journal is of interest and resulting in the expected metabolic profile. We would like to point out that these mice might also be extremely useful as a precision medicine model of mild Mahvash disease, a rare hereditary pancreatic neuroendocrine tumor syndrome characterized by inactivating mutations in the glucagon receptor. Further characterization of pancreas morphology and histology in the GcgrV369M+/+ mice at more advanced ages will be critically important to understand mild Mahvash disease in humans.

OIL OR FLAXSEED FLOUR REDUCES PANCREATIC ISLET AREA BUT DOES NOT AFFECT SERUM INSULIN, AT WEANING, IN MALE WISTAR RATS

The aim of the present study evaluated the influence of oil or flaxseed flour in pancreas morphology of pups, whose mothers were fed with oil or flaxseed flour during lactation, at weaning. After birth, the lactating rat males were randomly assigned: control (C, n=12 pups), flaxseed oil (FO, n=12 pups) and flaxseed flour (FF, n=12). At 21 days, the pups were weaning and anesthetized. Body mass, length, serum glucose, insulin, pancreas mass and pancreatic islet area were assessed. FO and FF showed higher (p<0.05) mass and length and lower glucose (p<0.05) when compared with C. Insulin (p=0.094) and pancreas mass (p=0.054) not differ between groups. FO and FF showed lower (p<0.05) pancreatic islet area when compared with C. A fed with FO or FF, during lactation may improve function pancreatic, as insulin sensitivity. These findings emphasize that oil or flaxseed flour during lactation may improve pancreatic function in early life.

Anti-Diabetic Effects of the Ethyl-Acetate Fraction of Trichilia catigua in Streptozo-tocin-Induced Type 1 Diabetic Rats

Background/Aims: Trichilia catigua A. Juss., known as “catuaba” in Brazil, has been popularly used as a tonic for fatigue, impotence and memory deficits. Previously, our group demonstrated that the ethyl-acetate fraction (EAF) of T. catigua has antioxidant and anti-inflammatory effects. The present study evaluated the anti-diabetic activity of EAF in type 1 diabetic rats. Methods: Male Wistar rats were divided into four groups (N: non-diabetic group, D: type 1 diabetic group, NC: non-diabetic + EAF group and DC: type 1 diabetic + EAF group). The latter two groups were treated with 200 mg/kg EAF. Type 1 diabetes was induced by intravenous streptozotocin (STZ) injection (35 mg/kg). Starting two days after STZ injection, EAF was administered daily by gavage for 8 weeks. Results: EAF attenuated body mass loss and reduced food and water intake. EAF improved hyperglycaemia and other biochemical parameters, such as alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, the number of pancreatic β-cells and the size of the islets had increased by β-cell proliferation in the DC group. EAF promoted reduction in kidney tissue damage in STZ-induced diabetic rats by reduction of renal fibrosis. Conclusion: The present study showed that EAF improves glucose homeostasis and endocrine pancreas morphology and inhibits the development of diabetic nephropathy in STZ-induced diabetic rats.

The gastrin-releasing peptide analog bombesin preserves exocrine and endocrine pancreas morphology and function during parenteral nutrition

Stimulation of digestive organs by enteric peptides is lost during total parental nutrition (PN). Here we examine the role of the enteric peptide bombesin (BBS) in stimulation of the exocrine and endocrine pancreas during PN. BBS protects against exocrine pancreas atrophy and dysfunction caused by PN. BBS also augments circulating insulin levels, suggesting an endocrine pancreas phenotype. While no significant changes in gross endocrine pancreas morphology were observed, pancreatic islets isolated from BBS-treated PN mice showed a significantly enhanced insulin secretion response to the glucagon-like peptide-1 (GLP-1) agonist exendin-4, correlating with enhanced GLP-1 receptor expression. BBS itself had no effect on islet function, as reflected in low expression of BBS receptors in islet samples. Intestinal BBS receptor expression was enhanced in PN with BBS, and circulating active GLP-1 levels were significantly enhanced in BBS-treated PN mice. We hypothesized that BBS preserved islet function indirectly, through the enteroendocrine cell-pancreas axis. We confirmed the ability of BBS to directly stimulate intestinal enteroid cells to express the GLP-1 precursor preproglucagon. In conclusion, BBS preserves the exocrine and endocrine pancreas functions during PN; however, the endocrine stimulation is likely indirect, through the enteroendocrine cell-pancreas axis.