The relationship between first-phase insulin secretion and glucose metabolism.
A possible pathogenetic link between absence of first-phase insulin secretion and development of impaired glucose metabolism has been suggested by the results of several cross-sectional studies. First-phase insulin secretion measured during a +7 mmol/l hyperglycemic glucose clamp correlated with total glucose disposal during the clamp (r = 0.65, p < 0.001, N = 59). To examine whether restoration of first-phase insulin secretion improves peripheral glucose uptake in subjects with impaired glucose utilization, seven insulin-resistant subjects (age 54 (38-62) years: BMI 29.3 (21.7-35.8); fasting plasma glucose 5.5 (4.8-7.2) mmol/l; fasting insulin 57 (37-105) pmol/l with impaired first-phase (148 (29-587) vs controls 485 (326-1086) pmol/l x 10 min; p < 0.05) and normal second-phase (1604 (777-4480) vs controls (1799 (763-2771) pmol/l x 110 min) insulin secretion were restudied. The impaired first-phase insulin secretion was restored by an iv insulin bolus at the start of the hyperglycemic clamp. Substrate oxidation rates and hepatic glucose production were determined by indirect calorimetry and [3-3H]glucose infusion. Total glucose uptake was impaired in the insulin-resistant subjects with impaired first-phase insulin secretion compared to controls (18.8 (13.2-22.2) vs 34.8 (24.3-62.1) mumol.kg-1 x min-1; p < 0.01). Restoration of first-phase insulin secretion (1467 (746-2440) pmol/l x 10 min) did not affect glucose uptake (20.2 (9.9-23.8) mumol.kg-1.min-1), with no difference in oxidative and non-oxidative glucose metabolism between the experiments. Second-phase insulin secretion was similar during both experiments.(ABSTRACT TRUNCATED AT 250 WORDS)
Widén
E I
EI
Fourth Department of Medicine, Helsinki University Hospital, Finland.
Eriksson
J G
JG
Ekstrand
A V
AV
Groop
L C
LC
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose