Captopril enhances insulin responsiveness of forearm muscle tissue in non‐insulin‐dependent diabetes mellitus

Abstract

Bradykinin infusion has been shown to improve glucose metabolism in non-insulin-dependent diabetic subjects (NIDD). Therefore, we tested the following hypothesis: inhibition of Kininase II, the bradykinin (BK) degrading enzyme, by captopril may also improve glucose metabolism in NIDD. Immediate effects of captopril on total body and peripheral glucose disposal were examined in five normotensive, normal weight NIDD and compared with five NIDD control subjects, well matched for age, weight and degree of fasting hyperglycaemia. The euglycaemic insulin clamp technique was employed in combination with the forearm catheter technique. After 90 min of insulin infusion a single dose of 25 mg captopril was administered orally, whereas in the control group a placebo was given. Captopril lead to a significant rise in total body glucose disposal and forearm glucose uptake, while in the control group no change was observed. Simultaneously, captopril lead to reduction in muscular release of lactate and pyruvate. We conclude that these results demonstrate the stimulatory effect of captopril on insulin-induced glucose disposal of the whole body, which appears to be a result of increased glucose utilization by peripheral tissues. Because of the described insulin-like activity of bradykinin, the concomitant accumulation of local kinins by captopril-induced inhibition of kininase II may represent an attractive hypothesis to explain the generated data sufficiently.

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

“…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).…”

Effects of 12 weeks of treatment with fermented milk on blood pressure, glucose metabolism and markers of cardiovascular risk in patients with type 2 diabetes: a randomised double-blind placebo-controlled study

“…2). Increased activity of the renin angiotensin system has been associated with obesity and glucose intolerance, and prospective epidemiological studies have reported that blocking the system using either ACE inhibitors or ARBs has been shown to reduce the incidence of diabetes (27,28,29,30) and both ACE-inhibitors and ARBs may improve insulin action to different extents (31,32) as well as insulin secretion (33). Accordingly, it may be considered biologically plausible that bioactive peptides in the Cardi04 yogurt inhibiting ACE may reduce plasma glucose levels in patients with diabetes.…”

The multi‐faceted cross‐talk between the insulin and angiotensin II signaling systems

“…In clinical practice, the beneficial effects of the use of ACEi and AT 1 blockers in patients with type 2 diabetes has been known for quite some time [43][44][45]. The overactivity of the RAS is likely to impair insulin signaling and contribute to the insulin resistance observed in essential hypertension [7].…”