Some Aspects of “Acute Phase” Insulin Release in Healthy Subjects

Abstract

The acute release of insulin in response to graded pulse doses of intravenous glucose was assessed in twelve healthy subjects before and during treatment with tolbutamide, ethanol and tolbutamide plus ethanol. A linear relationship was observed between the mean 3′-5′ insulin increment (ΔIRI) and the glucose dose up to five gm.; thereafter, the response plateaued. Insulin increments over baseline prior to treatment ranged from 12 ± 1.8 μU./ml. for 1.0 gm. to 124 ± 11.3 μU./ml. (mean ± S.E.M.) for 20.0 gm. Pretreatment with tolbutamide, ethanol and tolbutamide plus ethanol resulted in protentiation of the acute phase insulin release and enhanced glucose disappearance with glucose doses of 10 gm. and less. With the 20 gm. glucose dose, no significant potentiation of insulin release nor enhancement of glucose disappearance could be demonstrated. Potentiation of insulin release by tolbutamide pretreatment also required administration of the drug on the day of the test. We suggest that studies involving the effects of agents on the dynamics of acute phase insulin response to glucose be done with glucose doses which produce submaximal β-cell stimulation.

Effects of the new oral hypoglycaemic agent nateglinide on insulin secretion in Type 2 diabetes mellitus

“…2. Similar effects on first phase insulin response to intravenous glucose have been reported in healthy volunteers with tolbutamide[14], and in Type 2 DM with both tolazamide[15] and gliclazide[16].…”

“…2. Similar effects on ®rst phase insulin response to intravenous glucose have been reported in healthy volunteers with tolbutamide [14], and in Type 2 DM with both tolazamide [15] and gliclazide [16]. Bakkali-Nadi et al [17] have reported from isolated rat islet studies that the insulinotropic effects of the meglitinide analogues are glucose-dependent.…”

Combination of alcohol and glucose consumption as a risk to induce reactive hypoglycemia

“…On the basis of previous findings made not only in healthy individuals 3,15 , but also in patients with type 1 or type 2 diabetes, several mechanisms for alcohol-induced hypoglycemia have been proposed. Namely, a reduction in glucose production in the liver as a result of a reduction in hepatic gluconeogenesis 2 and/or glycogenolysis 16 , an increase in insulin secretion 3,4 , a reduction in intestinal glucose absorption 3,17,18 , and a suppression of growth hormone secretion 19 . Although insulin resistance in peripheral tissues is increased by long-term alcohol intake 20,21 , no significant differences were identified at the 15or 30-min time points in the II, Matsuda Index or the disposition index between the OGTT and OGATT in the present study, which suggests that insulin secretion and resistance do not change in the first 30 min after alcohol loading.…”

“…Alcohol consumption has been well known to be associated with hypoglycemia 1 . In previous studies, the hypoglycemic mechanism of alcohol has been described as a decline in hepatic gluconeogenesis 2 and/or an increase in insulin secretion 3,4 . Furthermore, some previous studies showed that alcohol consumption increases peripheral insulin resistance 5,6 , whereas others have made the seemingly contradictory findings of greater insulin secretion 3,7 or lower insulin resistance [8][9][10][11][12] .…”