ISSN:
1432-0428
Keywords:
Glucose cycle
;
insulin resistance
;
Type 2 (non-insulin-dependent) diabetes mellitus
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary 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·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 μmol·kg−1·min−1, p〈0.05) and during the 0.4 mU insulin infusion (10.1±1.3 vs 5.2±0.3 μmol·kg−1·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 μmol·kg−1·min−1, p〈0.05) but not during the 0.4 mU insulin infusion (2.0±0.4 vs 2.0±0.3 μmol·kg−1·min−1). During the 2.0 mU insulin infusion endogenous glucose production was suppressed to a similar degree in both groups (2.6±0.5 vs 3.4±0.7 μmol · kg−1·min−1) but glucose disappearance was lower in the diabetic subjects (30.8±2.0 vs 52.4±4.6 μmol·kg−1·min−1, p〈0.01). During the 2.0 mU insulin infusion glucose/glucose 6-phosphate cycling was greater in the diabetic subjects (3.8±0.7 vs 0.8±0.6 μmol·kg−1·min−1, p〈0.05). In conclusion, both hepatic and peripheral insulin action are impaired in Type 2 diabetes. Increased glucose/glucose 6-phosphate cycling is seen in the post-absorptive state and also during marked hyperinsulinaemia, when insulin resistance is predominantly due to reduced peripheral tissue glucose uptake.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00400689
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