Metabolic effects of IGF-I in diabetic rats

Luciano Rossetti, Simona Frontoni, Richard Dimarchi, Ralph A Defronzo, Andrea Giaccari

Research output: Contribution to journalArticle

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Abstract

Insulinlike growth factor I (IGF-I) stimulates glucose utilization (GU) in nondiabetic rats. We compared the effects of IGF-I and insulin on glucose metabolism in control (fed plasma glucose 7.7 ± 0.1 mM, n = 30) and partially (90%) pancreatectomized diabetic (plasma glucose 18.4 ± 0.8 mM, n = 30) awake unstressed rats. IGF-I was infused at 0.65 or 1.96 nmol · kg-1 · min-1 and insulin at 22 or 29 pmol · kg-1 · min-1 in combination with [3-3H]glucose while euglycemia was maintained by a variable glucose infusion. In controls, GU during the 0.65- and 1.96-nmol · kg-1 · min-1 IGF-I infusions (127 ± 7 and 168 ± 4 μmol · kg-1 · min-1, respectively) was similar to rates observed during the 22- and 29-pmol · kg-1 · min-1 insulin infusions (121 ± 2 and 156 ± 5 μmol · kg-1 · min-1). Whole-body glycolytic rate (3H2O generation) and muscle glycogen synthetic rate were identical during insulin and IGF-I infusions. In diabetic rats, GU was reduced by 30% versus control rats (P < 0.01) during both the low-dose (88 ± 7 vs. 121 ± 7 μmol · kg-1 · min-1) and higher-dose (109 ± 4 vs. 156 ± 5 μmol · kg-1 · min-1) insulin clamps. The defect in insulin action involved both muscle glycogen synthesis and glycolysis. In diabetic rats, IGF-I elicited rates of GU similar to controls (115 ± 10 and 164 ± 12 μmol kg-1 · min-1 during the 0.65- and 1.96-nmol · kg-1 · min-1 infusions, respectively) and corrected the intracellular defects in glycogen synthesis and glycolysis. To determine whether the effects of IGF-I and insulin are additive in stimulating GU, euglycemic clamps were performed with supramaximal concentrations of insulin, and IGF-I was superimposed during the last 100 min. In control rats, GU during insulin alone (191 ± 11 μmol · kg-1 · min-1) was identical to that during combined insulin plus IGF-I (198 ± 9 μmol · kg-1 · min-1), whereas in diabetic rats, GU rose from 155 ± 8 (insulin alone) to 200 ± 5 (insulin + IGF-I) μmol · kg-1 · min-1 (P < 0.01). Our conclusions are that 1) in control rats, the effects of IGF-I and insulin on total-body glucose metabolism and the major intracellular pathways of glucose disposal are identical, 2) in control rats, no additive effect of the two hormones is observed, 3) in diabetic rats, insulin-mediated total glucose uptake and intracellular glucose metabolism (glycolysis and glycogen synthesis) are markedly impaired, and 4) in diabetic rats, IGF-I but not insulin is capable of reversing the cellular defects in insulin action. These results indicate that the metabolic response to IGF-I is intact in insulin-resistant diabetic rats and that the potency of IGF-I differs in control and diabetic rats.

Original languageEnglish (US)
Pages (from-to)444-448
Number of pages5
JournalDiabetes
Volume40
Issue number4
StatePublished - Apr 1991

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Intercellular Signaling Peptides and Proteins
Insulin
Glucose
Glycogen
Glycolysis
Muscles
Glucose Clamp Technique
Hormones

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Rossetti, L., Frontoni, S., Dimarchi, R., Defronzo, R. A., & Giaccari, A. (1991). Metabolic effects of IGF-I in diabetic rats. Diabetes, 40(4), 444-448.

Metabolic effects of IGF-I in diabetic rats. / Rossetti, Luciano; Frontoni, Simona; Dimarchi, Richard; Defronzo, Ralph A; Giaccari, Andrea.

In: Diabetes, Vol. 40, No. 4, 04.1991, p. 444-448.

Research output: Contribution to journalArticle

Rossetti, L, Frontoni, S, Dimarchi, R, Defronzo, RA & Giaccari, A 1991, 'Metabolic effects of IGF-I in diabetic rats', Diabetes, vol. 40, no. 4, pp. 444-448.
Rossetti L, Frontoni S, Dimarchi R, Defronzo RA, Giaccari A. Metabolic effects of IGF-I in diabetic rats. Diabetes. 1991 Apr;40(4):444-448.
Rossetti, Luciano ; Frontoni, Simona ; Dimarchi, Richard ; Defronzo, Ralph A ; Giaccari, Andrea. / Metabolic effects of IGF-I in diabetic rats. In: Diabetes. 1991 ; Vol. 40, No. 4. pp. 444-448.
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abstract = "Insulinlike growth factor I (IGF-I) stimulates glucose utilization (GU) in nondiabetic rats. We compared the effects of IGF-I and insulin on glucose metabolism in control (fed plasma glucose 7.7 ± 0.1 mM, n = 30) and partially (90{\%}) pancreatectomized diabetic (plasma glucose 18.4 ± 0.8 mM, n = 30) awake unstressed rats. IGF-I was infused at 0.65 or 1.96 nmol · kg-1 · min-1 and insulin at 22 or 29 pmol · kg-1 · min-1 in combination with [3-3H]glucose while euglycemia was maintained by a variable glucose infusion. In controls, GU during the 0.65- and 1.96-nmol · kg-1 · min-1 IGF-I infusions (127 ± 7 and 168 ± 4 μmol · kg-1 · min-1, respectively) was similar to rates observed during the 22- and 29-pmol · kg-1 · min-1 insulin infusions (121 ± 2 and 156 ± 5 μmol · kg-1 · min-1). Whole-body glycolytic rate (3H2O generation) and muscle glycogen synthetic rate were identical during insulin and IGF-I infusions. In diabetic rats, GU was reduced by 30{\%} versus control rats (P < 0.01) during both the low-dose (88 ± 7 vs. 121 ± 7 μmol · kg-1 · min-1) and higher-dose (109 ± 4 vs. 156 ± 5 μmol · kg-1 · min-1) insulin clamps. The defect in insulin action involved both muscle glycogen synthesis and glycolysis. In diabetic rats, IGF-I elicited rates of GU similar to controls (115 ± 10 and 164 ± 12 μmol kg-1 · min-1 during the 0.65- and 1.96-nmol · kg-1 · min-1 infusions, respectively) and corrected the intracellular defects in glycogen synthesis and glycolysis. To determine whether the effects of IGF-I and insulin are additive in stimulating GU, euglycemic clamps were performed with supramaximal concentrations of insulin, and IGF-I was superimposed during the last 100 min. In control rats, GU during insulin alone (191 ± 11 μmol · kg-1 · min-1) was identical to that during combined insulin plus IGF-I (198 ± 9 μmol · kg-1 · min-1), whereas in diabetic rats, GU rose from 155 ± 8 (insulin alone) to 200 ± 5 (insulin + IGF-I) μmol · kg-1 · min-1 (P < 0.01). Our conclusions are that 1) in control rats, the effects of IGF-I and insulin on total-body glucose metabolism and the major intracellular pathways of glucose disposal are identical, 2) in control rats, no additive effect of the two hormones is observed, 3) in diabetic rats, insulin-mediated total glucose uptake and intracellular glucose metabolism (glycolysis and glycogen synthesis) are markedly impaired, and 4) in diabetic rats, IGF-I but not insulin is capable of reversing the cellular defects in insulin action. These results indicate that the metabolic response to IGF-I is intact in insulin-resistant diabetic rats and that the potency of IGF-I differs in control and diabetic rats.",
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T1 - Metabolic effects of IGF-I in diabetic rats

AU - Rossetti, Luciano

AU - Frontoni, Simona

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N2 - Insulinlike growth factor I (IGF-I) stimulates glucose utilization (GU) in nondiabetic rats. We compared the effects of IGF-I and insulin on glucose metabolism in control (fed plasma glucose 7.7 ± 0.1 mM, n = 30) and partially (90%) pancreatectomized diabetic (plasma glucose 18.4 ± 0.8 mM, n = 30) awake unstressed rats. IGF-I was infused at 0.65 or 1.96 nmol · kg-1 · min-1 and insulin at 22 or 29 pmol · kg-1 · min-1 in combination with [3-3H]glucose while euglycemia was maintained by a variable glucose infusion. In controls, GU during the 0.65- and 1.96-nmol · kg-1 · min-1 IGF-I infusions (127 ± 7 and 168 ± 4 μmol · kg-1 · min-1, respectively) was similar to rates observed during the 22- and 29-pmol · kg-1 · min-1 insulin infusions (121 ± 2 and 156 ± 5 μmol · kg-1 · min-1). Whole-body glycolytic rate (3H2O generation) and muscle glycogen synthetic rate were identical during insulin and IGF-I infusions. In diabetic rats, GU was reduced by 30% versus control rats (P < 0.01) during both the low-dose (88 ± 7 vs. 121 ± 7 μmol · kg-1 · min-1) and higher-dose (109 ± 4 vs. 156 ± 5 μmol · kg-1 · min-1) insulin clamps. The defect in insulin action involved both muscle glycogen synthesis and glycolysis. In diabetic rats, IGF-I elicited rates of GU similar to controls (115 ± 10 and 164 ± 12 μmol kg-1 · min-1 during the 0.65- and 1.96-nmol · kg-1 · min-1 infusions, respectively) and corrected the intracellular defects in glycogen synthesis and glycolysis. To determine whether the effects of IGF-I and insulin are additive in stimulating GU, euglycemic clamps were performed with supramaximal concentrations of insulin, and IGF-I was superimposed during the last 100 min. In control rats, GU during insulin alone (191 ± 11 μmol · kg-1 · min-1) was identical to that during combined insulin plus IGF-I (198 ± 9 μmol · kg-1 · min-1), whereas in diabetic rats, GU rose from 155 ± 8 (insulin alone) to 200 ± 5 (insulin + IGF-I) μmol · kg-1 · min-1 (P < 0.01). Our conclusions are that 1) in control rats, the effects of IGF-I and insulin on total-body glucose metabolism and the major intracellular pathways of glucose disposal are identical, 2) in control rats, no additive effect of the two hormones is observed, 3) in diabetic rats, insulin-mediated total glucose uptake and intracellular glucose metabolism (glycolysis and glycogen synthesis) are markedly impaired, and 4) in diabetic rats, IGF-I but not insulin is capable of reversing the cellular defects in insulin action. These results indicate that the metabolic response to IGF-I is intact in insulin-resistant diabetic rats and that the potency of IGF-I differs in control and diabetic rats.

AB - Insulinlike growth factor I (IGF-I) stimulates glucose utilization (GU) in nondiabetic rats. We compared the effects of IGF-I and insulin on glucose metabolism in control (fed plasma glucose 7.7 ± 0.1 mM, n = 30) and partially (90%) pancreatectomized diabetic (plasma glucose 18.4 ± 0.8 mM, n = 30) awake unstressed rats. IGF-I was infused at 0.65 or 1.96 nmol · kg-1 · min-1 and insulin at 22 or 29 pmol · kg-1 · min-1 in combination with [3-3H]glucose while euglycemia was maintained by a variable glucose infusion. In controls, GU during the 0.65- and 1.96-nmol · kg-1 · min-1 IGF-I infusions (127 ± 7 and 168 ± 4 μmol · kg-1 · min-1, respectively) was similar to rates observed during the 22- and 29-pmol · kg-1 · min-1 insulin infusions (121 ± 2 and 156 ± 5 μmol · kg-1 · min-1). Whole-body glycolytic rate (3H2O generation) and muscle glycogen synthetic rate were identical during insulin and IGF-I infusions. In diabetic rats, GU was reduced by 30% versus control rats (P < 0.01) during both the low-dose (88 ± 7 vs. 121 ± 7 μmol · kg-1 · min-1) and higher-dose (109 ± 4 vs. 156 ± 5 μmol · kg-1 · min-1) insulin clamps. The defect in insulin action involved both muscle glycogen synthesis and glycolysis. In diabetic rats, IGF-I elicited rates of GU similar to controls (115 ± 10 and 164 ± 12 μmol kg-1 · min-1 during the 0.65- and 1.96-nmol · kg-1 · min-1 infusions, respectively) and corrected the intracellular defects in glycogen synthesis and glycolysis. To determine whether the effects of IGF-I and insulin are additive in stimulating GU, euglycemic clamps were performed with supramaximal concentrations of insulin, and IGF-I was superimposed during the last 100 min. In control rats, GU during insulin alone (191 ± 11 μmol · kg-1 · min-1) was identical to that during combined insulin plus IGF-I (198 ± 9 μmol · kg-1 · min-1), whereas in diabetic rats, GU rose from 155 ± 8 (insulin alone) to 200 ± 5 (insulin + IGF-I) μmol · kg-1 · min-1 (P < 0.01). Our conclusions are that 1) in control rats, the effects of IGF-I and insulin on total-body glucose metabolism and the major intracellular pathways of glucose disposal are identical, 2) in control rats, no additive effect of the two hormones is observed, 3) in diabetic rats, insulin-mediated total glucose uptake and intracellular glucose metabolism (glycolysis and glycogen synthesis) are markedly impaired, and 4) in diabetic rats, IGF-I but not insulin is capable of reversing the cellular defects in insulin action. These results indicate that the metabolic response to IGF-I is intact in insulin-resistant diabetic rats and that the potency of IGF-I differs in control and diabetic rats.

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