Effects of Hypophysectomy and the Insulin-Like and Anti-Insulin Pituitary Peptides on Carbohydrate Metabolism in Yellow Avy/A (BALB/c x VY)F1 Hybrid Mice

Abstract

The amino-terminal portion of human growth hormone, residues 1-43 (hGHi-43), has insulin-potentiating action, while a hyperglycemic pituitary peptide (HP), which co-purifies with human growth hormone (hGH), is antagonistic to the action Of insulin. The effects of hGH, hGHi-43, and HP on glucose metabolism were assessed in young (4-5 weeks) and adult (6-8 months) hypophysectomized yellow AvY/A mice which lacked any interfering endogenous pituitary hormones, and compared with age-matched intact obese yellow AYY/A and lean agouti A/a mice. Treatment with hGH1-43 or HP did not promote body growth in hypophysectomized yellow mice; but after 2 weeks of treatment with hGH, there was a significant increase in body weight (P e 0.05). Treatment with HP raised blood glucose and lowered insulin concentrations in obese yellow mice, but not in agouti or hypophysectomized yellow mice. The severely impaired glucose tolerance of the hypophysectomized yellow mice was improved by acute (60 min) and chronic (3 days) treatment with hGH, -, , as well as by 2 weeks of treatment with hGH; in contrast, HP had no effect. Glucose oxidation in adipose tissue from obese yellow mice was low and showed essentially no response to stimulation by insulin at doses lower than 1000 microunits/ml. Basal glucose oxidation rates in adipose tissue taken from agouti and hypophysectomized yellow mice were significantly higher (P < 0.001) than those in tissue from obese yellow mice, and the rates responded significantly (P < 0.05) to 100 microunits/ml insulin. The insulin binding affinities in liver membranes from agouti mice were higher than those from either obese or hypophysectomized yellow mice. The insulin receptor densities were similar in both agouti and obese yellow mice, but higher in hypophysectomized yellow mice (P e 0.05). Treatment with hGHi-43 slightly increased, although not significantly, the insulin receptor density in yellow obese mice while hGH showed essentially no change. Therefore, hypophysectomy appeared to increase tissue response and decrease insulin resistance by increasing receptor numbers and lowering the circulating insulin levels. Furthermore, the insulin-like action of hGH was elicited directly in vivo by hGHi-43 in hypophysectomized yellow mice. [P.S.E.B.M. 1989[P.S.E.B.M. , Vol 1911 T T u m a n growth hormone (hGH or hGH22k) is known to promote body growth and to show H insulin-like and anti-insulin actions in rodents.

Limited Proteolysis of Human Growth Hormone at Low pH: Isolation, Characterization, and Complementation of the Two Biologically Relevant Fragments 1−44 and 45−191

“…The hypothesis was advanced that hGH may require proteolytic cleavage to exert its full biological potency. Indeed, the hGH molecule appears to be a prohormone (6,7), since a variety of hGH fragments, produced in vivo or in vitro by proteolysis of the hormone (9)(10)(11)(12)(13)(14)(15)(16)(17)(18) or prepared by chemical synthesis (19,20), have been shown to possess important biological activities. It has been reported that hGH is hydrolyzed by plasmin and thrombin at the level of the chain segment 134-149 and this gives rise to nicked forms of hGH still exhibiting growthpromoting activity (5,21).…”

Rodent models for the study of type 2 diabetes in children (juvenile diabesity)

“…The T2DM syndrome driven by mutations at the A locus is very complex, with important contributions from multiple endocrine glands. Removal of the adrenal glands prevents hyperglycemia and reduces obesity and hypophysectomy ablates the diabetes and the hyperinsulinemia but has only a small effect on the level of obesity (51–53).…”