Insulin signaling in the whole spectrum of GH deficiency

Abstract

GH is one of the insulin counterregulatory hormones which acts in the opposite way to insulin, increasing the glucose production by the liver and kidneys and decreasing glucose uptake from peripheral tissues, thus being a hyperglycemic hormone. When in excess, as in acromegaly, it induces glucose intolerance and diabetes. As expected, patients with GH deficiency (GHD) have hypoglycemia, especially in early childhood, but as GH is also a lipolytic hormone, these patients are becoming obese with higher percentages of body fat. Although obesity in general is directly related to insulin resistance, in patients with GH secretion disorders this relationship may be altered. In acromegaly there is a decrease in fat mass with worsening insulin sensitivity and mice with isolated GHD are characterized by greater insulin sensitivity despite excess fat mass. In humans with GHD, body composition shows increased body fat and decreased free fat mass, but the results regarding insulin sensitivity are still controversial in these patients. These discrepant results regarding insulin sensitivity in patients with GHD suggest the existence of other variables influencing these results. In the present review, we will try to follow the path of the different researches conducted on this subject, both in animal and human models, with the goal of understanding the current knowledge of insulin sensitivity across the spectrum of GHD.

Management of hypopituitarism: a perspective from the Brazilian Society of Endocrinology and Metabolism

“…Hypopituitarism may be associated with several metabolic and cardiovascular comorbidities, such as hypertension, unfavorable changes in body composition (with increased total and abdominal fat associated with decreased lean mass), and decreased exercise capacity, which may be accompanied by dyslipidemia, insulin resistance, premature atherosclerosis, and cardiac dysfunction (1,(4)(5)(6). Insulin sensitivity varies greatly among patients with hypopituitarism, depending on numerous factors such as the etiology and treatment of the underlying cause, obesity, severity of pituitary deficiency, and inadequate hormone replacement (31). Metabolic syndrome, as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III criteria, has been observed in roughly 40% of the adult patients with hypopituitarism, and is associated with an increased risk of diabetes and vascular events (12,(32)(33)(34).…”

The Interaction of Insulin and Pituitary Hormone Syndromes

“…Whereas GH deficiency according to the negative effects of elevated GH levels on glucose homeostasis would be expected to result in beneficial effects the findings of available studies on this topic are inconsistent. Normal, reduced as well as increased insulin sensitivity have been reported in GH deficient patients (55,56). GH deficiency in adults has been reported to induce insulin resistance by inhibiting glucose storage rate and glycogen synthase activity in peripheral tissues (57).…”

The role of glucose and insulin in the metabolic regulation of growth hormone secretion

“…При акромегалии наблюдается снижение количества жировой массы и повышение инсулинорезистентности, а мыши с изолированным дефицитом ГР характеризуются лучшей чувствительностью к инсулину, несмотря на избыток жировой массы. У людей с дефицитом ГР определяется увеличение количества жировых отложений в составе тела и уменьшение массы свободного жира, но результаты относительно чувствительности к инсулину противоречивы, так как предполагается существование других факторов, влияющих на инсулинорезистентность [48].…”