Studies of pancreatic islet microcirculation and insulin secretion in normal and diabetic rats
Year: 2007
Type: dissertation
Abstract: Type 2 diabetes is increasing globally. The disease is characterized not\nonly by hyperglycemia, but also by insulin resistance with attendant\ndyslipidemia, hypertension and endothelial dysfunction. These aberrations\nmay result in macrovascular disease, and deeply impact the longevity and\nquality of life in diabetic patients. Gender differences also exist with\nmore pronounced negative effects of diabetes on the lipid profile and\nblood pressure in women compared with men. To well control all of these\nrisk factors, diabetic patients frequently need to be treated with a\nlipid lowering statin, and an ACE inhibitor or angiotensin receptor\nantagonist against hypertension and/or albuminuria. Such drugs reportedly\nalso decrease the risk of incident diabetes in clinical trials, by\nunknown mechanisms. The aim of the present work was to characterize the\neffects of vasoactive drugs, free fatty acids and ethanol on islet\nmicrocirculation, in vivo insulin secretion and glucose tolerance in\nnormal and diabetic rats of both genders. To this end, a microsphere\ntechnique was evaluated and applied for measurements of islet blood flow\nin rats. Vasoactive drugs that are frequently given to diabetic patients\nwere found to increase islet blood flow (IBF), augment insulin secretion\nand improve glycemia. This suggests that a local pancreatic RAS plays a\nsubstantial role in the regulation of islet microcirculation, thereby\nimpacting insulin secretion and glucose tolerance. Qualitative and\nquantitative gender-specific differences in responses to such drugs were\nnoted, which may be due to the vasoactive features of sex hormones or\nother influences conferred by gender. Free fatty acids lowered IBF and\nmay thus worsen hyperglycemia by limiting the supply of insulin needed to\ncurb hyperglycemia. Alternatively, the decreased IBF could represent a\nprotective mechanism by which islet exposure to free fatty acid toxicity\ncan be limited. Ethanol acutely exerted substantial influences on\npancreatic microcirculation by evoking a massive redistribution of\npancreatic blood flow from the exocrine into the endocrine part via\nmechanisms mediated by nitric oxide and vagal stimuli, augmenting late\nphase insulin secretion, and thereby evoking hypoglycemia. This effect\nmay in part underlie the well known hypoglycemic properties of alcohol in\ndiabetic patients or in alcoholics with hepatic failure. Collectively,\nthese direct islet effects of RAS-interfering drugs, statins, fatty acids\nand ethanol may prove valuable in designing different and gender-specific\ntreatment strategies for diabetic patients or subjects at risk of\ndeveloping glucose intolerance. Moreover, vasoactive drugs that are\nfrequently given to diabetic patients may confer additional treatment\nbenefits beyond their systemic effects by increasing islet blood flow,\naugmenting insulin secretion and improving glycemia.
Source: Figshare
Author: Huang Zhen
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2146877763