Glucose production and gluconeogenesis in postabsorptive and starved normal and streptozotocin-diabetic rats.
Using a 3-hour primed-continuous infusion of [3-3H]glucose and [2-13C]glycerol, we measured glucose production, gluconeogenesis from glycerol, and total gluconeogenesis (using mass isotopomer distribution analysis [MIDA] of glucose) in postabsorptive and starved normal and streptozotocin-diabetic rats. In normal rats, 48 hours of starvation increased (P < .01) the percent contribution of both gluconeogenesis from glycerol (from 14.4% +/- 1.8% to 25.5% +/- 4.0%) and total gluconeogenesis (from 52.2% +/- 3.9% to 89.8% +/- 1.3%) to glucose production, but the absolute gluconeogenic fluxes were not modified, since glucose production decreased. Diabetic rats showed increased glucose production in the postabsorptive state; this decreased with starvation and was comparable to the of controls after 48 hours of starvation. Gluconeogenesis was increased in postabsorptive diabetic rats (69.0% +/- 1.3%, P < .05 v controls). Surprisingly, this contribution of gluconeogenesis to glucose production was not found to be increased in 24-hour starved diabetic rats (64.4% +/- 2.4%). These rats had significant liver glycogen stores, but gluconeogenesis was also low (42.8% +/- 2.1%) in 48-hour starved diabetic rats deprived of glycogen stores. Moreover, in 24-hour starved diabetic rats infused with [3-13C]lactate, gluconeogenesis was 100% when determined by comparing circulating glucose and liver pyruvate enrichment, but only 47% +/- 3% when calculated from the MIDA of glucose. Therefore, MIDA is not a valid method to measure gluconeogenesis in starved diabetic rats. This was not explained by differences in the labeling of liver and kidney triose phosphates: functional nephrectomy of starved diabetic rats decreased glucose production, but gluconeogenesis calculated by the MIDA method was only 48% +/- 3.3%. We conclude that (1) diabetic rats have increased glucose production and gluconeogenesis in the postabsorptive state; (2) starvation decreases glucose production and increases the contribution of gluconeogenesis, but MIDA is not an appropriate method in this situation; and (3) the kidneys contribute to glucose production in starved diabetic rats.
Peroni
O
O
Laboratoire de Physiologie Métabolique et Rénale, Faculté R. Laennec, Lyon, France.
Large
V
V
Diraison
F
F
Beylot
M
M
D000818:Animals; D002247:Carbon Isotopes; D015331:Cohort Studies; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D005943:Gluconeogenesis / Q000502:physiology*; D005947:Glucose / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism*; D005990:Glycerol / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism; D007262:Infusions, Intravenous; D007408:Intestinal Absorption / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013217:Starvation / Q000378:metabolism*; D013997:Time Factors; D014316:Tritium
D002247:Carbon Isotopes; D014316:Tritium; D005947:Glucose; D005990:Glycerol