Abnormal renal, hepatic, and muscle glucose metabolism following glucose ingestion in type 2 diabetes.
Recent studies indicate an important role of the kidney in postprandial glucose homeostasis in normal humans. To determine its role in the abnormal postprandial glucose metabolism in type 2 diabetes mellitus (T2DM), we used a combination of the dual-isotope technique and net balance measurements across kidney and skeletal muscle in 10 subjects with T2DM and 10 age-, weight-, and sex-matched nondiabetic volunteers after ingestion of 75 g of glucose. Over the 4.5-h postprandial period, diabetic subjects had increased mean blood glucose levels (14.1 +/- 1.1 vs. 6.2 +/- 0.2 mM, P < 0.001) and increased systemic glucose appearance (100.0 +/- 6.3 vs. 70.0 +/- 3.3 g, P < 0.001). The latter was mainly due to approximately 23 g greater endogenous glucose release (39.8 +/- 5.9 vs. 17.0 +/- 1.8 g, P < 0.002), since systemic appearance of the ingested glucose was increased by only approximately 7 g (60.2 +/- 1.4 vs. 53.0 +/- 2.2 g, P < 0.02). Approximately 40% of the diabetic subjects' increased endogenous glucose release was due to increased renal glucose release (19.6 +/- 3.1 vs. 10.6 +/- 2.4 g, P < 0.05). Postprandial systemic tissue glucose uptake was also increased in the diabetic subjects (82.3 +/- 4.7 vs. 69.8 +/- 3.5 g, P < 0.05), and its distribution was altered; renal glucose uptake was increased (21.0 +/- 3.5 vs. 9.8 +/- 2.3 g, P < 0.03), whereas muscle glucose uptake was normal (18.5 +/- 1.8 vs. 25.9 +/- 3.3 g, P = 0.16). We conclude that, in T2DM, 1) both liver and kidney contribute to postprandial overproduction of glucose, and 2) postprandial renal glucose uptake is increased, resulting in a shift in the relative importance of muscle and kidney for glucose disposal. The latter may provide an explanation for the renal glycogen accumulation characteristic of diabetes mellitus as well as a mechanism by which hyperglycemia may lead to diabetic nephropathy.
Meyer
Christian
C
Department of Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA. christian.meyer@med.va.gov
Woerle
Hans J
HJ
Dostou
Jean M
JM
Welle
Stephen L
SL
Gerich
John E
JE
D000284:Administration, Oral; D001158:Arteries; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D005260:Female; D005542:Forearm; D005943:Gluconeogenesis; D005947:Glucose / Q000008:administration & dosage* / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009994:Osmolar Concentration
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose