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IGF-I treatment in adults with type 1 diabetes: effects on glucose and protein metabolism in the fasting state and during a hyperinsulinemic-euglycemic amino acid clamp.

Carroll, PV, Christ, ER, Umpleby, AM, Gowrie, I, Jackson, N, Bowes, SB, Hovorka, R, Croos, P, Sönksen, PH and Russell-Jones, DL (2000) IGF-I treatment in adults with type 1 diabetes: effects on glucose and protein metabolism in the fasting state and during a hyperinsulinemic-euglycemic amino acid clamp. Diabetes, 49 (5). pp. 789-796.

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Abstract

Type 1 diabetes is associated with abnormalities of the growth hormone (GH)-IGF-I axis. Such abnormalities include decreased circulating levels of IGF-I. We studied the effects of IGF-I therapy (40 microg x kg(-1) x day(-1)) on protein and glucose metabolism in adults with type 1 diabetes in a randomized placebo-controlled trial. A total of 12 subjects participated, and each subject was studied at baseline and after 7 days of treatment, both in the fasting state and during a hyperinsulinemic-euglycemic amino acid clamp. Protein and glucose metabolism were assessed using infusions of [1-13C]leucine and [6-6-2H2]glucose. IGF-I administration resulted in a 51% rise in circulating IGF-I levels (P < 0.005) and a 56% decrease in the mean overnight GH concentration (P < 0.05). After IGF-I treatment, a decrease in the overnight insulin requirement (0.26+/-0.07 vs. 0.17+/-0.06 U/kg, P < 0.05) and an increase in the glucose infusion requirement were observed during the hyperinsulinemic clamp (approximately 67%, P < 0.05). Basal glucose kinetics were unchanged, but an increase in insulin-stimulated peripheral glucose disposal was observed after IGF-I therapy (37+/-6 vs. 52+/-10 micromol x kg(-1) x min(-1), P < 0.05). IGF-I administration increased the basal metabolic clearance rate for leucine (approximately 28%, P < 0.05) and resulted in a net increase in leucine balance, both in the basal state and during the hyperinsulinemic amino acid clamp (-0.17+/-0.03 vs. -0.10+/-0.02, P < 0.01, and 0.25+/-0.08 vs. 0.40+/-0.06, P < 0.05, respectively). No changes in these variables were recorded in the subjects after administration of placebo. These findings demonstrated that IGF-I replacement resulted in significant alterations in glucose and protein metabolism in the basal and insulin-stimulated states. These effects were associated with increased insulin sensitivity, and they underline the major role of IGF-I in protein and glucose metabolism in type 1 diabetes.

Item Type: Article
Authors :
NameEmailORCID
Carroll, PVUNSPECIFIEDUNSPECIFIED
Christ, ERUNSPECIFIEDUNSPECIFIED
Umpleby, AMUNSPECIFIEDUNSPECIFIED
Gowrie, IUNSPECIFIEDUNSPECIFIED
Jackson, Nn.jackson@surrey.ac.ukUNSPECIFIED
Bowes, SBUNSPECIFIEDUNSPECIFIED
Hovorka, RUNSPECIFIEDUNSPECIFIED
Croos, PUNSPECIFIEDUNSPECIFIED
Sönksen, PHUNSPECIFIEDUNSPECIFIED
Russell-Jones, DLUNSPECIFIEDUNSPECIFIED
Date : May 2000
Uncontrolled Keywords : Adult, Amino Acids, Circadian Rhythm, Diabetes Mellitus, Type 1, Electrolytes, Fasting, Female, Glucose, Glucose Clamp Technique, Human Growth Hormone, Humans, Hyperinsulinism, Hypoglycemic Agents, Insulin, Insulin-Like Growth Factor I, Male, Middle Aged, Parenteral Nutrition Solutions, Proteins, Solutions
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 09:32
Last Modified : 17 May 2017 14:43
URI: http://epubs.surrey.ac.uk/id/eprint/824103

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