A nonsuppressible increase of glucagon secretion by isolated islets of high-protein-fed rats

Abstract

We recently demonstrated increased plasma glucagon but nomal insulin in rats fed a high-protein, carbohydrate-free (HP) diet; however, other investigators have reported that both plasma glucagon and insulin are increased after protein feeding. For this reason, we have investigated the ffects of an HP diet on pancreatic secretion of insulin and glucagon. Male rats were fed an HP or control diet for one, three, or five days, and, at the end of the feeding period, blood was taken for glucose, insulin, and glucagon determinations. Additional animals fed the HP and control diets for up to 10 days were sacrificed, the pancreases removed, and islets of Langerhans isolated. Islets were incubated for 30 minutes in media with glucose concentration of1.7, 8.3, 16.7, or 33.4 mM. Insulin and glucagon secreted into the media were determined by radioimmunoassay. Plasma insulin was markedly reduced after one day of HP feeding but gradually returned to normal by the fifth day. Plasma glucagon was not altered on day 1 but was significantly increased after three days of HP feeding. The I/G molar ratio, which declined precipitously on day 1, increased thereafter but, as shown previously, remained at a level that promotes gluconeogenesis for up to 10 days. Insulin secretion by isolated islets of control and HP rats increased more than 10-fold as medium glucose was raised from 1.7 to 16.7 mM. There was no difference in insulin release by the two groups of islets. Glucagon secretion by HP islest at low medium glucose remained normal during the first five days; however, beginning on day 3 there was gradual loss of the suppressive effect of high medium glucose on glucagon secretion. After one week of HP feeding, glucagon secretion at low medium glucose was doubled and there was complete lack of suppression of the elevated hormone production by high medium glucose. The alterations of alpha-cell function induced by HP feeding are similar to those found in human and experimental diabetes.