Effects of Fasting on Insulin Secretion, Islet Glucose Metabolism, and the Cyclic Adenosine 3',5'-Monophosphate Content of Rat Pancreatic Islets In Vitro

Abstract

Fasting for 24 hours inhibits glucose-induced insulin secretion from isolated rat pancreatic islets. At glucose 15 raM the inhibition is only present during the initial 30-45 minutes of stimulation. It decreases at higher glucose concentrations and disappears at glucose 37.5 mM. In islets of fed rats, 15 minutes of stimulation with glucose 15 mM induced an almost threefold rise of islet cyclic adenosine 3',5'-monophosphate (cAMP). Both this effect and the secretory response were inhibited by about 65 per cent after 24 hours of fasting and almost completely by 72 hours of food deprivation. Fasting for 24 hours also caused a 56 per cent inhibition of the rise of islet cAMP and insulin secretion induced by D-glyceraldehyde 10 mM, but the inhibition was not further enhanced by 72 hours of fasting. Fasting for 24 and 72 hours did not significantly inhibit the islet cAMP response to 15 minutes of stimulation with glucose 37.5 mM. Fasting for 24 hours impaired neither islet glucose oxidation (14CO2 production) nor over-all glucose utilization (production of 3H-water from [5-3H] glucose) during the initial 30 minutes of stimulation with glucose. After 72 hours of fasting, both over-all glucose utilization and glucose oxidation were reduced by 25 per cent. These findings suggest that inhibition of the islet cAMP response is a primary factor in the early (24 hours) fasting-induced impairment of the insulin secretory response to glucose stimulation at 5-15 mM. Inhibition of islet glucose metabolism seems to be an independent additional phenomenon that becomes manifest after longer periods of food deprivation.

Reduced insulin secretion after short-term food deprivation in rats plays a key role in the adaptive interaction of glucose and free fatty acid utilization

“…It is likely that this is caused not only by mechanisms which remove insulin from the circulation, but also by a decreased responsiveness of the B-cells [4,10,25]. We focussed our attention on basal insulin levels which are supposed to be a function of secretory responsiveness [8].…”

“…Blood glucose Free fatty acids Food deprivation Insulin secretion IN vitro and in vivo studies of insulin secretion have shown that the insulin secretory response to glucose is markedly reduced in the fasted state [4,21,22,25]. The mechanism for this phenomenon has been studied in detail and there is evidence that decreased c-AMP formation from ATP is involved [4,25].…”

“…The mechanism for this phenomenon has been studied in detail and there is evidence that decreased c-AMP formation from ATP is involved [4,25]. It is also known that fasting over 24 hr is accompanied by a decrease in blood glucose and an increment in plasma free fatty acids (FFA) [13,18].…”

Banting Lecture 2001

“…Alternatively, they might be internally available to the ␤-cell, perhaps by liberation from a storage pool of TG as a result of cAMP-mediated activation of hormone-sensitive lipase (HSL). In this regard, it is noteworthy that islets have been shown to contain HSL (67) and are known to display an increase in cAMP content in response to elevated glucose concentrations (68). If this were true, the absolute requirement for exogenous FFA for GSIS in the fasted state might be ascribed to depletion of the ␤-cell's TG reserve and/or to blunting of its cAMP response to glucose (68).…”

Fatty acids, lipotoxicity and insulin secretion

“…An attractive possibility would be, however, that in the fed state the beta cell contains adequate amounts of the fatty acid-derived component that synergizes with glucose and other secretagogues to elicit insulin secretion, but that this becomes depleted during fasting and is functionally replaced by the increased plasma NEFA concentration. Whether a fasting-induced reduction in glucose metabolism, e. g. a fall in the activity of glucokinase [47], phosphofractokinase [48], pyruvate dehydrogenase [49] or in the glucose-mediated increase of beta-cell cyclic AMP accumulation [50] is an additional factor also warrants further investigation. (Fig.…”