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Skeletal muscle capillary responses to insulin are abnormal in late-stage diabetes and are restored by angiotensin-converting enzyme inhibition.

Author	Lucy H Clerk, Michelle A Vincent, Eugene J Barrett, Miles F Lankford, Jonathan R Lindner
Citation Information	American journal of physiology. Endocrinology and metabolism, 293:E1804-9 (2007)
Keywords	Angiotensin-Converting Enzyme Inhibitors, Animals, Blood Glucose, Blood Pressure, Blood Volume, Capillaries, Diabetes Mellitus, Type 2, Erythrocyte Deformability, Glucose Clamp Technique, Hindlimb, Hypoglycemic Agents, Insulin, Muscle, Skeletal, Polyuria, Rats, Rats, Mutant Strains, Rats, Zucker, Regional Blood Flow, Tetrahydroisoquinolines, Ultrasonography, Doppler, Color
Applications	Immunohistochemistry (Paraffin)
Species:	Rat
Related Products	MAB1393
Pub Med ID	17911341

Acute physiological hyperinsulinemia increases skeletal muscle capillary blood volume (CBV), presumably to augment glucose and insulin delivery. We hypothesized that insulin-mediated changes in CBV are impaired in type 2 diabetes mellitus (DM) and are improved by angiotensin-converting enzyme inhibition (ACE-I). Zucker obese diabetic rats (ZDF, n = 18) and control rats (n = 9) were studied at 20 wk of age. One-half of the ZDF rats were treated with quinapril (ZDF-Q) for 15 wk prior to study. CBV and capillary flow in hindlimb skeletal muscle were measured by contrast-enhanced ultrasound (CEU) at baseline and at 30 and 120 min after initiation of a euglycemic hyperinsulinemic clamp (3 mU.min(-1).kg(-1)). At baseline, ZDF and ZDF-Q rats were hyperglycemic and hyperinsulinemic vs. controls. Glucose utilization in ZDF rats was 60-70% lower (P 0.05) than in controls after 30 and 120 min of hyperinsulinemia. In ZDF-Q rats, glucose utilization was impaired at 30 min but similar to controls at 120 min. Basal CBV was lower in ZDF and ZDF-Q rats compared with controls (13 +/- 4, 7 +/- 3, and 9 +/- 2 U, respectively). With hyperinsulinemia, CBV increased by about twofold in control animals at 30 and 120 min, did not change in ZDF animals, and increased in ZDF-Q animals only at 120 min to a level similar to controls. Anatomic capillary density on immunohistology was not different between groups. We conclude that insulin-mediated capillary recruitment in skeletal muscle, which participates in glucose utilization, is impaired in animals with DM and can be partially reversed by chronic ACE-I therapy.