Short-Term Metabolic Effects of Recombinant Human Insulin-like Growth Factor I in Healthy Adults

Abstract

Insulin-like growth factor I (IGF I) is structurally similar to insulin and shares many of its biologic properties. We compared the short-term metabolic effects of recombinant IGF I (100 micrograms [13.3 nmol] per kilogram of body weight) and insulin (0.15 IU [1 nmol] per kilogram) in eight healthy volunteers (four men and four women). The hypoglycemic responses to both hormones were nearly identical in the doses used. The lowest blood glucose levels were reached after 30 minutes: 1.98 +/- 0.44 mmol per liter after IGF I and 1.78 +/- 0.29 after insulin. On a molar basis, IGF I was only 6 percent as potent as insulin in the production of hypoglycemia. Insulin also inhibited lipolysis more effectively than IGF I. Levels of epinephrine, norepinephrine, growth hormone, glucagon, and cortisol responded similarly to both agents. The hypoglycemia produced by IGF I is probably due to the supraphysiologic concentrations of the free peptide that result from its rapid intravenous injection. Fifteen minutes after injection, the serum level of IGF I increased from 144 +/- 38 ng per milliliter at base line to 424 +/- 56, of which 80 percent was free in the plasma (not bound to IGF carrier proteins). The determination of whether any of the short-term metabolic effects of IGF I have any clinical application will require further investigation.

The Emerging Role of the Insulin-Like Growth Factor Pathway as a Therapeutic Target in Cancer

“…The mechanism of the hyperglycemia is not completely understood, but data that link the IGF-I ligand system and glucose metabolism may provide clues to the metabolic effects of anti-IGF-IR therapy. IGF-I administration in humans results in hypoglycemia, decreased serum levels of fatty acids, and increased lipogenesis [81,82]. Recombinant IGF increases insulin sensitivity in the liver and muscle in patients with type II diabetes mellitus and results in better glucose control [83].…”

Liver-Derived IGF-I is of Importance for Normal Carbohydrate and Lipid Metabolism

“…I GF-I promotes growth and differentiation in a variety of tissues (1). IGF-I also mimics some of the metabolic actions of insulin, including stimulation of glucose and amino acid uptake and inhibition of gluconeogenesis (2)(3)(4). These effects are largely mediated by the IGF-I receptor, although IGF-I can also bind to the insulin receptor with low affinity (5,6).…”

“…One may speculate that the primary role of liver-derived IGF-I is the regulation of carbohydrate and lipid metabolism, rather than growth promotion. Clinical studies of short-term metabolic effects of recombinant human IGF-I (rhIGF-I) in healthy adults have shown that IGF-I is 6% as potent as insulin on a molar basis in the production of hypoglycemia (2). A patient with severe IGF-I deficiency (secondary to a homozygous deletion of a part of the IGF-I gene) had insulin resistance that was normalized by treatment with rhIGF-I (11).…”

“…The crown-rump length was measured on the same DXA scan as the body fat, and it was defined as the distance between the crown of the skull and a point located in the middle of a line between the two caput femora. The BMI was then calculated as the body weight in grams/(crown-rump length in millimeters) 2 . The retroperitoneal and gonadal fat depots were dissected and weighed (wet weight).…”

Insulin‐like growth factor II stimulates glucose transport in human skeletal muscle

“…The IGF-I and IGF-II polypeptides are insulin-like growth factors which have structural homology with insulin [I], Although the major effects of the IGF's are on cell replication and differentiation [I ,2], the IGF's demonstrate effects similar to insulin on glucose metabolism [3,4]. IGF-I exerts a stimulatory effect on glucose transport in rat 141 and human skeletal muscle [S].…”