Insulin Sensitivity in Obese Hypertensive Dyslipidemic Patients Treated with Enalapril or Atenolol

Morel, Yannis; Gadient, A; Keller, U; Vadas, L.; Golay, Alain

doi:10.1097/00005344-199508000-00017

Cited by 40 publications

(23 citation statements)

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“…In addition to the amelioration of insulin secretion through the increased islet blood flow induced by an ACE inhibitor, as seen in this study, the blockade of the RAS during the development of diabetes has been attributed to improvements in peripheral insulin sensitivity and b-cell dysfunction (30,31). ACE inhibitors have been shown to improve whole-body and skeletal muscle insulin resistance in hypertensive subjects with or without type 2 diabetes (32)(33)(34)(35)(36)(37)(38)(39)(40). The reduction of angiotensin II-mediated vascular resistance by ACE inhibition may improve insulin-stimulated glucose transport activity in skeletal muscle (41).…”

Section: Discussionmentioning

confidence: 81%

Insulin Receptor Substrate-2 (Irs2) in Endothelial Cells Plays a Crucial Role in Insulin Secretion

et al. 2014

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Endothelial cells are considered to be essential for normal pancreatic β-cell function. The current study attempted to demonstrate the role of insulin receptor substrate-2 (Irs2) in endothelial cells with regard to insulin secretion. Endothelial cell–specific Irs2 knockout (ETIrs2KO) mice exhibited impaired glucose-induced, arginine-induced, and glucagon-induced insulin secretion and showed glucose intolerance. In batch incubation and perifusion experiments using isolated islets, glucose-induced insulin secretion was not significantly different between the control and the ETIrs2KO mice. In contrast, in perfusion experiments, glucose-induced insulin secretion was significantly impaired in the ETIrs2KO mice. The islet blood flow was significantly impaired in the ETIrs2KO mice. After the treatment of these knockout mice with enalapril maleate, which improved the islet blood flow, glucose-stimulated insulin secretion was almost completely restored to levels equal to those in the control mice. These data suggest that Irs2 deletion in endothelial cells leads to a decreased islet blood flow, which may cause impaired glucose-induced insulin secretion. Thus, Irs2 in endothelial cells may serve as a novel therapeutic target for preventing and ameliorating type 2 diabetes and metabolic syndrome.

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Section: Discussionmentioning

confidence: 81%

Insulin Receptor Substrate-2 (Irs2) in Endothelial Cells Plays a Crucial Role in Insulin Secretion

et al. 2014

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“…Furthermore, the peripheral vasodilatory actions of ACE inhibitors (through diverse mechanisms, including prostaglandin and nitric oxide) lead to an improvement in skeletal muscle blood flow, the primary target for insulin action and an important determinant of glucose uptake. 27 Clinical evidence supporting this effect has been provided by Morel and coworkers, 28 who have shown improved insulin sensitivity when enalapril was given for 12 weeks to 14 obese, hypertensive, and dyslipidemic patients. A similar effect has also been reported with captopril.…”

Section: Discussionmentioning

confidence: 93%

Enalapril Reduces the Incidence of Diabetes in Patients With Chronic Heart Failure

et al. 2003

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Background-Diabetes mellitus is a predictor of morbidity and mortality in patients with heart failure. The effect of angiotensin-converting enzyme (ACE) inhibitors on the prevention of diabetes in patients with left ventricular dysfunction is unknown. The aim of this retrospective study was to assess the effect of the ACE inhibitor enalapril on the incidence of diabetes in the group of patients from the Montreal Heart Institute enrolled in the Studies of Left Ventricular Dysfunction (SOLVD). Methods and Results-Clinical charts were evaluated for fasting plasma glucose (FPG) levels by blinded reviewers. A diagnosis of diabetes was made when a FPG Ն126 mg/dL (7 mmol/L) was found at 2 visits (follow-up, 2.9Ϯ1.0 years). Of the 391 patients enrolled at the Montreal Heart Institute, 291 were not diabetic (FPG Ͻ126 mg/dL without a history of diabetes), 153 of these were on enalapril and 138 were on placebo. Baseline characteristics were similar in the 2 groups. Forty patients developed diabetes during follow-up, 9 (5.9%) in the enalapril group and 31 (22.4%) in the placebo group (PϽ0.0001). By multivariate analysis, enalapril remained the most powerful predictor for risk reduction of developing diabetes (hazard ratio, 0.22; 95% confidence intervals, 0.10 to 0.46; PϽ0.0001).

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“…In addition, the inhibition of angiotensin II generation is followed by a signi®cant improvement in insulin sensitivity, 35 ± 37 while b-blockers, such as atenolol, can even worsen the insulin resistance. 36 The alpha-1 receptor and calcium entry blockers are ef®-cient in lowering blood pressure in the hypertensive obese, without making the lipid and carbohydrate metabolic abnormalities worse. 1,6,7 Some reports even suggested that these agents may improve insulin sensitivity.…”

Section: Therapeutic Conclusionmentioning

confidence: 99%

“…6 These agents may also make insulin resistance worse, especially when associated with thiazide diuretics. 1,7,36 …”

Section: Therapeutic Conclusionmentioning

confidence: 99%

Obesity and hypertension: from pathophysiology to treatment

Kolanowski

1999

Int J Obes

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While the prevalence of hypertension is clearly increased among the overweight persons, the pathophysiological mechanisms underlying this frequent association of obesity and hypertension are still poorly understood. The expansion of extracellular volume, inducing hypervolaemia and increased cardiac output, represents the characteristic haemodynamic feature of the obesity-related hypertension. The maintenance of hypervolemia in the face of elevated blood pressure, indicates a resetting of pressor natriuresis toward higher blood pressure. The development of hypertension also indicates an increase in peripheral vascular resistance, thus the lack of physiological adaptation of peripheral resistance to increased cardiac output. The mechanisms underlying these changes in renal function and vascular reactivity can no longer be attributed to hyperinsulinaemia as such, but might be related to insulin resistance responsible for the enhancement in pressor activity of noradrenaline and angiotensin II. This increased reactivity to pressor factors may be due to an inadequate nitric oxide generation by vascular endothelium and to increased sodium and calcium concentration in vascular smooth muscle cells. The role of increased neuropeptide Y (NPY) activity, may also be involved. As to enhancement of tubular sodium reabsorption, it could be related to histological changes within the renal medulla, leading to compression of tubules and vasa recta, hence a more ef®cient sodium reabsorption. As to the therapeutic approach, the low-energy sodium-restricted diet associated with increased physical activity, represents the cornerstones of treatment for the obesity-related hypertension. If this approach fails, the pharmacological treatment becomes necessary, and the use of the converting enzyme inhibitors seems to be the most appropriate choice of drug therapy for hypertensive obese patients.

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Insulin Sensitivity in Obese Hypertensive Dyslipidemic Patients Treated with Enalapril or Atenolol

Cited by 40 publications

References 0 publications

Insulin Receptor Substrate-2 (Irs2) in Endothelial Cells Plays a Crucial Role in Insulin Secretion

Insulin Receptor Substrate-2 (Irs2) in Endothelial Cells Plays a Crucial Role in Insulin Secretion

Enalapril Reduces the Incidence of Diabetes in Patients With Chronic Heart Failure

Obesity and hypertension: from pathophysiology to treatment

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