The mechanisms of insulin sensitivity improving effects of angiotensin converting enzyme inhibitor.
It is well-known that angiotensin converting enzyme (ACE) inhibitor not only decreases blood pressure (BP) but also improves insulin sensitivity. To elucidate the mechanisms of these actions of ACE inhibitor, we evaluated its effect on both BP and insulin sensitivity (M-value) as estimated by the glucose clamp technique in essential hypertensives in comparison with the effect of angiotensin receptor (AT) antagonist. We also evaluated the effect of ACE inhibitor on BP, M-value and muscle fiber composition in fructose-fed rats (FFR) as an insulin-resistant hypertensive model with or without treatment with Hoe 140 (kinin receptor antagonist). In essential hypertensives, both ACE inhibitor and AT antagonist decreased BP and improved insulin sensitivity to the same extent. In FFR, ACE inhibitor also decreased BP and improved insulin sensitivity. Moreover, Hoe 140 showed no effect on these actions of ACE inhibitor. The composite ratio of type I fiber of soleus muscle was decreased significantly in FFR compared to control and ACE inhibitor produced a recovery of the composite ratio of type I fiber to the same as control. These results suggested that muscle fiber composition of skeletal muscle is linked to insulin resistance, and that ACE inhibitor may modulate muscle fiber composition through its vasodilative effect in hypertension. These results also suggest that for vasodilation, it is more important to inhibit angiotensin II than to block degradation of kinins or to improve insulin sensitivity by ACE inhibitor.
Ura
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The Second Department of Internal Medicine, Sapporo Medical University, School of Medicine, Japan.
Higashiura
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Shimamoto
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K
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004032:Diet; D005632:Fructose / Q000008:administration & dosage; D015309:Glucose Clamp Technique; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000187:drug effects; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D011945:Receptors, Angiotensin; D005632:Fructose