Type 2 diabetes impairs splanchnic uptake of glucose but does not alter intestinal glucose absorption during enteral glucose feeding: additional evidence for a defect in hepatic glucokinase activity.
We have previously reported that splanchnic glucose uptake, hepatic glycogen synthesis, and hepatic glucokinase activity are decreased in people with type 2 diabetes during intravenous glucose infusion. To determine whether these defects are also present during more physiological enteral glucose administration, we studied 11 diabetic and 14 nondiabetic volunteers using a combined organ catheterization-tracer infusion technique. Glucose was infused into the duodenum at a rate of 22 micromol. kg(-1). min(-1) while supplemental glucose was given intravenously to clamp glucose at approximately 10 mmol/l in both groups. Endogenous hormone secretion was inhibited with somatostatin, and insulin was infused to maintain plasma concentrations at approximately 300 pmol/l (i.e., twofold higher than our previous experiments). Total body glucose disappearance, splanchnic, and leg glucose extractions were markedly lower (P < 0.01) in the diabetic subjects than in the nondiabetic subjects. UDP-glucose flux, a measure of glycogen synthesis, was approximately 35% lower (P < 0.02) in the diabetic subjects than in the nondiabetic subjects. This was entirely accounted for by a decrease (P < 0.01) in the contribution of extracellular glucose because the contribution of the indirect pathway to hepatic glycogen synthesis was similar between groups. Neither endogenous and splanchnic glucose productions nor rates of appearance of the intraduodenally infused glucose in the portal vein differed between groups. In summary, both muscle and splanchnic glucose uptake are impaired in type 2 diabetes during enteral glucose administration. The defect in splanchnic glucose uptake appears to be due to decreased uptake of extracellular glucose, implying decreased glucokinase activity. Thus, abnormal hepatic and muscle (but not gut) glucose metabolism are likely to contribute to postprandial hyperglycemia in people with type 2 diabetes.
Basu
A
A
Division of Endocrinology, Metabolism and Nutrition, Mayo Clinic and Foundation, 200 1st St, SW, Rochester, MN 55905, USA.
Basu
R
R
Shah
P
P
Vella
A
A
Johnson
C M
CM
Jensen
M
M
Nair
K S
KS
Schwenk
W F
WF
Rizza
R A
RA
D000042:Absorption; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004386:Duodenum; D004750:Enteral Nutrition; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007267:Injections; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood; D007413:Intestinal Mucosa / Q000378:metabolism*; D007866:Leg / Q000098:blood supply; D008099:Liver / Q000378:metabolism; D008875:Middle Aged; D011169:Portal Vein; D012016:Reference Values; D014530:Uridine Diphosphate / Q000378:metabolism; D014535:Uridine Diphosphate Glucuronic Acid / Q000652:urine; D014781:Viscera / Q000378:metabolism*
D001786:Blood Glucose; D007328:Insulin; D014535:Uridine Diphosphate Glucuronic Acid; D014530:Uridine Diphosphate; D005941:Glucokinase; D005947:Glucose