Effects of Growth Hormone and Free Fatty Acids on Insulin Sensitivity in Patients with Type 1 Diabetes
Open Access
- 1 September 2009
- journal article
- research article
- Published by The Endocrine Society in Journal of Clinical Endocrinology & Metabolism
- Vol. 94 (9), 3297-3305
- https://doi.org/10.1210/jc.2009-0378
Abstract
Context: Because GH stimulates lipolysis, an increase in circulating free fatty acid levels, as opposed to a direct effect of high GH levels, could underlie the development of insulin resistance in type 1 diabetes (T1D). Our aim was to explore the relative contributions of GH and free fatty acids to the development of insulin resistance in patients with T1D. Patients: Seven (four females, three males) nonobese patients with T1D aged 21–30 yr were studied on four occasions in random order. On each visit, overnight endogenous GH production was suppressed by octreotide. Three 1-h pulses of recombinant human GH (rhGH) or placebo were administered on two visits each. Acipimox, an antilipolytic drug, or a placebo were ingested every 4 h on two visits each. Stable glucose and glycerol isotopes were used to assess glucose and glycerol turnover. The overnight protocol was concluded by a two-step hyperinsulinemic euglycemic clamp on each visit. Main Outcome: rhGH administration led to increases in the insulin infusion rate required to maintain euglycemia overnight (P = 0.008), elevated basal endogenous glucose production (P = 0.007), decreased basal peripheral glucose uptake (P = 0.03), and reduced glucose uptake during step 1 of the clamp (P < 0.0001). Coadministration of rhGH and acipimox reversed these effects and suppression of lipolysis in the absence of GH replacement led to further increases in insulin sensitivity. Results: GH pulses were associated with an increase in endogenous glucose production and decreased rates of peripheral glucose uptake, which was entirely reversed by acipimox. Therefore, GH-driven decreases in insulin sensitivity are mainly determined by the effect of GH on lipolysis. Growth hormone decreases insulin sensitivity through increases in free fatty acid levels.Keywords
This publication has 56 references indexed in Scilit:
- Effects on insulin secretion and insulin action of a 48-h reduction of plasma free fatty acids with acipimox in nondiabetic subjects genetically predisposed to type 2 diabetesAmerican Journal of Physiology-Endocrinology and Metabolism, 2007
- Paradoxical Changes in Muscle Gene Expression in Insulin-Resistant Subjects After Sustained Reduction in Plasma Free Fatty Acid ConcentrationDiabetes, 2007
- Insulin resistance in type 1 diabetesDiabetes/Metabolism Research and Reviews, 2002
- Natural course of growth hormone hypersecretion in insulin-dependent diabetes mellitusMedical Hypotheses, 1996
- Mechanisms of fatty acid-induced inhibition of glucose uptake.JCI Insight, 1994
- The frequency and amplitude of growth hormone secretory episodes as determined by deconvolution analysis are increased in adolescents with insulin dependent diabetes mellitus and are unaffected by short‐term euglycaemiaClinical Endocrinology, 1993
- Effects of a physiological growth hormone pulse on substrate metabolism in insulin-dependent (type 1) diabetic subjectsJournal of Clinical Endocrinology & Metabolism, 1992
- Effect of Human Growth Hormone on Muscle and Adipose Tissue Metabolism in the Forearm of Man *JCI Insight, 1965
- The Effect of Nicotinic Acid on the Plasma Free Fatty Acids Demonstration of a Metabolic Type of SympathicolysisActa Medica Scandinavica, 1962