Skeletal muscle capillary responses to insulin are abnormal in late-stage diabetes and are restored by angiotensin-converting enzyme inhibition.
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.
Clerk
Lucy H
LH
Division of Endocrinology, University of Virginia Health System, Charlottesville, Virginia.
Vincent
Michelle A
MA
Barrett
Eugene J
EJ
Lankford
Miles F
MF
Lindner
Jonathan R
JR
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001810:Blood Volume / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D004907:Erythrocyte Deformability / Q000187:drug effects; D015309:Glucose Clamp Technique; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000503:physiopathology; D011141:Polyuria / Q000652:urine; D000077583:Quinapril; D051381:Rats; D011922:Rats, Mutant Strains; D011924:Rats, Zucker; D012039:Regional Blood Flow / Q000187:drug effects; D044005:Tetrahydroisoquinolines / Q000494:pharmacology / Q000627:therapeutic use; D018615:Ultrasonography, Doppler, Color
D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D044005:Tetrahydroisoquinolines; D000077583:Quinapril