Abstract
Hypertension often occurs in conjunction with insulin resistance. The purpose of this study was to evaluate whether sustained renal hypertension increases the risk of diabetes mellitus in rats, and to define the underlying mechanisms. Two‐kidney, one‐clip hypertensive (2K1C) rats received captopril (50 mg/kg/day), α‐lipoic acid (100 mg/kg/day), or vehicle treatment for 3 months after surgery. Blood pressure was measured by tail cuff plethysmography. Oral glucose tolerance test (OGTT), immunohistochemistry, and western blotting were performed. In addition, insulin secretion from islet cells was measured. OGTT yielded abnormal results, and the number of islet cells and the size of pancreatic β/α cells were decreased in 2K1C rats. Basal insulin levels were also reduced in the plasma. Insulin secretion from pancreatic islet cells in response to high glucose was also attenuated in 2K1C rats compared with sham rats. The levels of oxidative stress markers, including 8‐hydroxydeoxyguanosine and NADPH oxidase‐4, were increased in pancreatic tissue and pancreatic islets in 2K1C rats. The abnormalities observed in 2K1C rats were improved by captopril or α‐lipoic acid treatment. These findings indicate that sustained renal hypertension may lead to pancreatic dysfunction, increasing oxidative stress in pancreatic islets.
Highlights
Hypertension and cardiovascular diseases are the leading causes of morbidity and mortality (Kannel and Wilson 1995)
The body weight of 2K1C rats was significantly reduced compared with sham rats (429.7 Æ 32.3 g vs. 492.7 Æ 12.2 g, P < 0.05). 2K1C rats with a Systolic blood pressure (SBP) of >140 mmHg were allocated to the hypertensive group
We have used a hypertension rat model to demonstrate that sustained hypertension induces abnormal islet morphology and insulin secretion in response to high glucose and increases oxidative stress in the pancreas
Summary
Hypertension and cardiovascular diseases are the leading causes of morbidity and mortality (Kannel and Wilson 1995). Hypertension often occurs in conjunction with insulin resistance (Carlsson et al 1998) and other components of the cardiometabolic syndrome (Cersosimo and DeFronzo 2006). Plays a pivotal role in the pathogenesis of hypertension and insulin resistance (Richey et al 1999; Ran et al 2006). Ang II suppresses adiponectin production, which impairs insulin sensitivity (Ran et al 2006). Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
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