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J Clin Endocrinol Metab. 2017 Apr 1;102(4):1340-1349. doi: 10.1210/jc.2016-3835.

Substrate Metabolism and Insulin Sensitivity During Fasting in Obese Human Subjects: Impact of GH Blockade.

Author information

1
Medical Research Laboratory, Department of Endocrinology and Internal Medicine.
2
Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark.
3
Department of Biomedicine and.
4
Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität, 80336 Munich, Germany.
5
The MR Research Center, and.
6
Department of Clinical Pharmacology, Aarhus University Hospital 8000 Aarhus, Denmark.

Abstract

Context:

Insulin resistance and metabolic inflexibility are features of obesity and are amplified by fasting. Growth hormone (GH) secretion increases during fasting and GH causes insulin resistance.

Objective:

To study the metabolic effects of GH blockade during fasting in obese subjects.

Subjects and Methods:

Nine obese males were studied thrice in a randomized design: (1) after an overnight fast (control), (2) after 72 hour fasting (fasting), and (3) after 72 hour fasting with GH blockade (pegvisomant) [fasting plus GH antagonist (GHA)]. Each study day consisted of a 4-hour basal period followed by a 2-hour hyperinsulinemic, euglycemic clamp combined with indirect calorimetry, assessment of glucose and palmitate turnover, and muscle and fat biopsies.

Results:

GH levels increased with fasting (P < 0.01), and the fasting-induced reduction of serum insulin-like growth factor I was enhanced by GHA (P < 0.05). Fasting increased lipolysis and lipid oxidation independent of GHA, but fasting plus GHA caused a more pronounced suppression of lipid intermediates in response to hyperinsulinemic, euglycemic clamp. Fasting-induced insulin resistance was abrogated by GHA (P < 0.01) primarily due to reduced endogenous glucose production (P = 0.003). Fasting plus GHA also caused elevated glycerol levels and reduced levels of counterregulatory hormones. Fasting significantly reduced the expression of antilipolytic signals in adipose tissue independent of GHA.

Conclusions:

Suppression of GH activity during fasting in obese subjects reverses insulin resistance and amplifies insulin-stimulated suppression of lipid intermediates, indicating that GH is an important regulator of substrate metabolism, insulin sensitivity, and metabolic flexibility also in obese subjects.

PMID:
28324055
DOI:
10.1210/jc.2016-3835
[Indexed for MEDLINE]

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