Mechanisms of postabsorptive hyperglycemia in streptozotocin diabetic rats.
Postabsorptive hepatic glucose output (HGO) was estimated in normal (n = 9) and streptozotocin (STZ) diabetic rats after a 6-h [3-3H]glucose infusion. In diabetic rats, HGO was estimated at ambient (n = 12) or normal (achieved via phlorizin infusion; n = 9) glucose concentrations. HGO was not statistically different between normal and diabetic rats (63 +/- 3 vs. 77 +/- 10 mumol.kg-1.min-1; P > 0.05). HGO was also normal in diabetic rats even when plasma glucose was normalized with phlorizin infusion (71 +/- 5 vs. 63 +/- 3 mumol.kg-1.min-1; P > 0.05). In contrast, peripheral glucose uptake, when estimated at matched euglycemia, was lower by approximately 25% in diabetic than in normal rate (46 +/- 6 vs. 62 +/- 3 mumol.kg-1.min-1; P < 0.01). In addition, acute changes in plasma glucose concentrations did not have significant effects on HGO or peripheral glucose uptake in diabetic rats (P > 0.05), resulting in markedly decreased glucose clearance at ambient hyperglycemia (P < 0.001). In conclusion, postabsorptive HGO was not elevated in a majority (17 of 21) of STZ diabetic rats with severe hyperglycemia and therefore was not responsible for postabsorptive hyperglycemia. Our data suggest that an impairment in the ability of glucose to regulate peripheral glucose uptake or HGO develops in STZ diabetes and contributes to postabsorptive hyperglycemia.
Wi
J K
JK
Department of Physiology and Biophysics, University of Southern California School of Medicine, Los Angeles 90033, USA.
Kim
J K
JK
Youn
J H
JH
D000042:Absorption; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006029:Glycosuria / Q000652:urine; D006943:Hyperglycemia / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D010695:Phlorhizin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D006003:Glycogen; D005934:Glucagon; D010695:Phlorhizin; D005947:Glucose