Glucose-6-phosphatase flux in vitro is increased in type 2 diabetes

Citation
Jn. Clore et al., Glucose-6-phosphatase flux in vitro is increased in type 2 diabetes, DIABETES, 49(6), 2000, pp. 969-974
Citations number
41
Categorie Soggetti
Endocrynology, Metabolism & Nutrition","Endocrinology, Nutrition & Metabolism
Journal title
DIABETES
ISSN journal
00121797 → ACNP
Volume
49
Issue
6
Year of publication
2000
Pages
969 - 974
Database
ISI
SICI code
0012-1797(200006)49:6<969:GFIVII>2.0.ZU;2-K
Abstract
Despite the effects of hyperinsulinemia and hyperglycemia, 2 factors known to inhibit endogenous glucose production (EGP) in nondiabetic subjects, inc reased EGP is a consistent feature of type 2 diabetes. Recent studies have suggested that increased glucose-6-phosphatase (G6Pase) and/or decreased gl ucokinase (GK) may explain the increase in EGP. However, no studies to date have clearly established this relationship in type 2 diabetes. The present studies were designed to determine rates of EGP and the activities of G6Pa se and GK in obese patients scheduled for gastric bypass surgery. The study group consisted of 14 obese nondiabetic subjects and 13 patients with type 2 diabetes (BMI 53.7 +/- 2.4 vs. 50.1 +/- 1.6 kg/m(2)). Rates of EGP were determined after an overnight fast with a 4-h infusion of [6,6]-D-glucose, and they were significantly higher in the type 2 diabetic patients (85.9 +/ - 10.0 vs. 137.8 +/- 14.4 mg . m(-2) . min(-1), P < 0.001) despite greater plasma glucose (5.1 +/- 0.1 vs. 12.0 +/- 1.1 mmol/l) and similar insulin co ncentrations (130.8 +/- 19.8 vs. 112.8 +/- 16.2 pmol/l, NS). Moreover, resi stance to insulin-induced suppression of EGP was observed in the patients w ith type 2 diabetes when insulin concentrations were increased from similar to 120 to 180 pmol/l. Hepatic G6Pase activity determined from freshly isol ated microsomes was significantly increased in the type 2 diabetic patients compared with the obese control subjects (0.16 +/- 0.02 vs, 0.09 +/- 0.01 mu mol . min(-1) . mg(-1) protein, P < 0.02), whereas levels of GK were dec reased (1.20 +/- 0.16 vs. 2.01 +/- 0.01 mu mol . min(-1) . mg(-1) protein, P < 0.01). Net flux through G6Pase was significantly increased in type 2 di abetic patients (P < 0.01). We conclude that increased EGP is mediated in p art by increased G6Pase flux in type 2 diabetes.