Plasma Catecholamines and Blood Substrate Concentrations: Studies in Insulin Induced Hypoglycaemia and after Adrenaline Infusions

Abstract

Plasma adrenaline-blood glucose interrelationships in insulin-induced hypoglycaemia in man have been studied using a sensitive double-isotope derivative method for adrenaline estimation. Plasma adrenaline reached a peak of 1.24 ng/ml at 45 minutes after insulin while blood glucose reached a nadir of 22 mg/100 ml at 30 minutes. There was a strong correlation both between the rise in adrenaline and the degree of hypoglycaemia and between the rise in adrenaline and the post-hypoglycaemic rise in glucose. Plasma noradrenaline rose from 0.29 to 0.59 ng/ml, the rise correlating with the rise in adrenaline. Changes in pulse rate preceded and were unrelated to changes in plasma catecholamines. Fuel mobilisation in response to adrenaline infusion (6 mug/min. for 20 min.) in normoglycaemic man was also studied. Plasma adrenaline concentration rose from a mean of 0.02 ng/ml to 0.71 ng/ml while plasma noradrenaline concentration was unchanged. Blood glucose rose from 71 to 98 mg/100 ml while plasma insulin decreased from 11 to 8 muU/ml. Blood lactate rose by 0.85 mM while pyruvate concentration remained unchanged. Blood glycerol concentration rose twofold and ketone body concentration threefold but there was little change in the concentrations of the glucogenic amino acids, alanine, glutamate and glutamine. Both the 3-hydroxybutyrate/acetoacetate ratio and the lactate/pyruvate ratio rose implying a more reduced intracellular state due presumably to increased hepatic fatty acid oxidation. It is concluded that adrenaline enhances the recycling of lactate and spares glucose through the mobilitsation of lipids but that amino acids are little affected.

The role of ?diabetogenic? hormones on carbohydrate and lipid metabolism following oral glucose loading in insulin dependent diabetics: Effects of acute hormone administration

“…The acute release of diabetogenic hormones in response to insulin-induced hypoglycaemia [10,19,20,40] has been presumed to contribute also to insulin resistance and impaired glucose tolerance with subsequent hyperglycaemia ("Somogyi effect") [41]. On the basis of the present results, it would seem that only catecholamines possess the potency to normalize rapidly blood glucose concentration after insulin-induced hypoglycaemia, whereas glucagon, cortisol, and growth hormone seem to be of no major relevance to the acute restoration of glucose homeostasis.…”

“…The delay in the development of ketoacidosis in insulin-withdrawn diabetics by either somatostatin-induced suppression of growth hormone and glucagon [17] or following pituitary ablation [1] serves as further support for implicating these hormones as pathogenic factors of deranged metabolic control. In addition, circulatory levels of the same hormones increase in response to insulin-induced hypoglycaemia [7,[18][19][20] raising the question of their relative impact as insulin antagonists in this condition.The present study was therefore undertaken to assess the effect of acutely increasing circulating levels of insulin-opposing hormones to levels reported in severe derangements of diabetic control and insulin-induced hypoglycaemia by examining their impact upon glucose disposal. For this purpose the amount of insulin required to assimilate an oral glucose load (50 g) was estimated by means of a glucose controlled insulin infusion system (artificial endocrine pancreas) [21] in insulin-dependent diabetics, who received short-term infusions of exogenous glucagon, cortisol, growth hormone and adrenaline.…”

“…The delay in the development of ketoacidosis in insulin-withdrawn diabetics by either somatostatin-induced suppression of growth hormone and glucagon [17] or following pituitary ablation [1] serves as further support for implicating these hormones as pathogenic factors of deranged metabolic control. In addition, circulatory levels of the same hormones increase in response to insulin-induced hypoglycaemia [7,[18][19][20] raising the question of their relative impact as insulin antagonists in this condition.…”

Physiological responses to insulin hypoglycaemia in spinal man

“…In normal subjects insulin hypoglycaemia is accompanied by a marked increase in plasma adrenaline levels (Goldfein et al, 1961;Christensen et al, 1975). A twofold rise in plasma noradrenaline also occurs.…”

Insulin Infusion in Conscious Dogs

“…These are thought to be caused by sympathetic stimulation resulting from insulin-induced hypoglycemia (10)(11)(12)(13). However, the cardiovascular effects of insulin cannot be entirely the consequence of hypoglycemia, as they occur even when the blood glucose concentration does not decline below normal fasting values (3,14). Furthermore, it has been shown that sympathetic stimulation, as evidenced by an increase in plasma norepinephrine, may occur after insulin administration even in the absence of hypoglycemia (14)(15)(16).…”