Contribution of glucose/glucose 6-phosphate cycle activity to insulin resistance in type 2 (non-insulin-dependent) diabetes mellitus.
It has been suggested that increased glucose/glucose 6-phosphate substrate cycling impairs net hepatic glucose uptake in Type 2 (non-insulin-dependent) diabetes mellitus and contributes to hyperglycaemia. To investigate glucose/glucose 6-phosphate cycle activity and insulin action in Type 2 diabetes we studied eight patients and eight healthy control subjects, using the euglycaemic glucose clamp and isotope dilution techniques with purified [2-3H]- and [6-3H] glucose tracers, in the post-absorptive state and eight patients and five healthy control subjects during consecutive insulin infusions at rates of 0.4 and 2.0 mU.kg-1 x min-1. [2-3H]glucose and [6-3H]glucose radioactivity in plasma samples were determined using selective enzymatic detritiation, allowing calculation of glucose turnover rates for each isotope, the difference being glucose/glucose 6-phosphate cycling. Endogenous glucose production ([6-3H]glucose) was greater in diabetic than control subjects in the post-absorptive state (15.6 +/- 1.5 vs 11.3 +/- 0.4 mumol.kg-1 x min-1, p < 0.05) and during the 0.4 mU insulin infusion (10.1 +/- 1.3 vs 5.2 +/- 0.3 mumol.kg-1 x min-1, p < 0.01) indicating hepatic insulin resistance. Glucose/glucose 6-phosphate cycling was significantly greater in diabetic than in control subjects in the post-absorptive state (2.6 +/- 0.4 vs 1.6 +/- 0.2 mumol.kg-1 x min-1, p < 0.05) but not during the 0.4 mU insulin infusion (2.0 +/- 0.4 vs 2.0 +/- 0.3 mumol.kg-1 x min-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Rooney
D P
DP
Sir George E. Clark Metabolic Unit, Royal Victoria Hospital, Belfast, UK.
Neely
R D
RD
Beatty
O
O
Bell
N P
NP
Sheridan
B
B
Atkinson
A B
AB
Trimble
E R
ER
Bell
P M
PM
D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000502:physiology*; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D006946:Hyperinsulinism / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D014316:Tritium
D005958:Glucosephosphates; D007328:Insulin; D014316:Tritium; D019298:Glucose-6-Phosphate; D005947:Glucose