title: Insulin-like growth factor-I and insulin have no differential effects on glucose production and utilization under conditions of hyperglycemia.
abstract: We have previously shown that in moderately hyperglycemic depancreatized dogs, a glucose-lowering infusion of insulin-like growth factor-I (IGF-I) increased glucose utilization and lactate more, and suppressed glucose production and lipolysis less, than an equipotent glucose-lowering dose of insulin. Similar differences have been observed by others in nondiabetic and diabetic rats. To determine whether the decline in glycemia was important in detecting differential effects of IGF-I and insulin on glucose turnover, IGF-I (0.43 micrograms/kg.min; n = 6) or insulin (0.9 mU/kg.min; n = 9) were infused for 180 min, while hyperglycemia (approximately 180 mg/dl) was maintained. The decline of plasma glucose specific activity was minimized by using the matched step tracer infusion ([6-3H]- and [2-3H]glucose) method. Our results confirmed the approximately 10% potency of IGF-I on glucose metabolism compared to insulin and the lack of effect of IGF-I on insulin clearance. Under conditions of hyperglycemia, the glucose turnover findings were unexpected; there was no difference in the inhibition of glucose production (difference from basal, 2.7 +/- 0.4 mg/kg.min with IGF-I and 2.4 +/- 0.2 with insulin) or the stimulation of glucose utilization (difference from basal, 4.5 +/- 0.8 mg/kg.min with IGF-I and 4.7 +/- 1.3 with insulin). However, lactate increased more (P < 0.01) with IGF-I (from 1230 +/- 163 to a peak of 1903 +/- 349 microM) than insulin (from 1209 +/- 291 to 1535 +/- 340 microM) despite the same increment in glucose utilization. FFA and glycerol declined more with insulin, but the difference was not significant. IGF-I and insulin suppressed plasma amino acids to an equivalent extent. We concluded that 1) the differential effects of IGF-I and insulin on glucose turnover are masked under conditions of hyperglycemia; and 2) because insulin and IGF-I induced the same increment in glucose utilization, but lactate increased more with IGF-I, IGF-I might affect intracellular glucose metabolism differently from insulin. The failure of IGF-I to induce greater glucose utilization than insulin during hyperglycemia, the greater rise in lactate with IGF-I treatment, and the absence of differential effects on proteolysis indicate that IGF-I might have only limited clinical application in the treatment of diabetes.
authors.affiliation: Department of Physiology, University of Toronto, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Giacca
authors.forename: S J
authors.initials: SJ
authors.lastname: Fisher
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Shi
authors.forename: R
authors.initials: R
authors.lastname: Gupta
authors.forename: H L
authors.initials: HL
authors.lastname: Lickley
authors.forename: A
authors.initials: A
authors.lastname: Skottner
authors.forename: G H
authors.initials: GH
authors.lastname: Anderson
authors.forename: S
authors.initials: S
authors.lastname: Efendic
authors.forename: M
authors.initials: M
authors.lastname: Vranic
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000097:blood; D006943:Hyperglycemia / Q000097:blood*; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male; D014316:Tritium
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007773:Lactates; D014316:Tritium; D019344:Lactic Acid; D007334:Insulin-Like Growth Factor I; D005947:Glucose; D005990:Glycerol