Metasomatotrophic diabetes and its induction: Basal insulin secretion and insulin release responses to glucose, glucagon, arginine and meals

Abstract

Growth hormone treatment produced somatotrophic diabetes, with hyperglycaemia, polyuria, glycosuria and elevation in serum non-esterified fatty acids (NEFA) in dogs. Early in this diabetes, fasting serum immunoreactive insulin (IRI) rose 20fold, the insulin/glucose (I/G) ratio rose 10-fold and in response to glucose infusion, the rise in IRI was twice the normal. In the latter half of the continued growth hormone treatment, the intensity of the diabetes increased, serum IRI declined to the normal level and the I/G ratio became subnormal. Late in the treatment, following glucose infusion, there was no change in serum IRI, no fall in NEFA and further depression of glucose tolerance. In metasomatotrophic diabetes, in which hyperglycaemia, glycosuria and high NEFA level persisted, fasting serum IRI was normal during several months, then became subnormal and the I/G ratio was diminished further. Following glucose IV there was no change in serum IRI, no fall in NEFA and low glucose tolerance. The normally-occurring rises in serum IRI following arginine and glucagon IV and after the ingestion of a meal were absent. These permanently diabetic dogs were responsive to insulin IV. The insulin content of the pancreas was reduced to about 1.2% of the normal after 14 months of this diabetes. From the sequence of change it is concluded that growth hormone induced metasomatotrophic diabetes by causing excessive secretion of insulin under basal and stimulative conditions, leading to permanent loss of function of the beta cells of the pancreatic islets, to such an extent that basal insulin secretion was low and the ability to secrete extra insulin in response to stimuli was lost.

Improved insulin sensitivity, preserved beta cell function and improved whole-body glucose metabolism after low-dose growth hormone replacement therapy in adults with severe growth hormone deficiency: a pilot study

“…High-dose growth hormone treatment increases insulin secretion associated with the early development of insulin resistance [46,47], whereas prolonged administration of growth hormone in high doses results in reduced insulin secretion despite increasing insulin resistance, leading to deteriorating glucose tolerance [47]. These data indicate that chronic supraphysiological doses of growth hormone accelerate insulin resistance, compensatory hyperinsulinaemia and subsequent beta cell failure, a feature resembling the long-term sequelae of altered glucose homeostasis in untreated acromegalic patients.…”

Impact of treatment with recombinant human GH and IGF-I on visceral adipose tissue and glucose homeostasis in adults

“…High-dose GH treatment increases insulin secretion, which is associated with the early development of insulin resistance [18], but prolonged GH administration results in reduced insulin secretion despite increasing insulin resistance, leading to deteriorating glucose tolerance [18]. These data indicate that chronic supraphysiological doses of GH accelerate insulin resistance, compensatory hyperinsulinemia, and subsequent b-cell ''failure,'' a feature resembling the long-term sequelae of altered glucose homeostasis in untreated acromegalic patients.…”

How safe is the treatment of uraemic children with recombinant human growth hormone?

“…The pathogenesis of acromegalic diabetes has been explained by the metabolic properties of GH, which inhibits glucose absorption by the musculature. Exogenous GH can provoke permanent diabetes mellitus in dogs receiving GH injections twice a day for 32-44 days [7]. Fasting glucose concentrations rose twofold within 2 weeks and fourfold at 1 month.…”

“…At the conclusion of GH treatment at approximately 1 month, there was no insulin response to various secretagogues and the glucose tolerance had further deteriorated. After 8-10 months, diabetes mellitus occurred which was characterized by a marked reduction in the insulin content of the pancreas [7,8].…”