Acute and Short-Term Administration of a Sulfonylurea (Gliclazide) Increases Pulsatile Insulin Secretion in Type 2 Diabetes

Abstract

The high-frequency oscillatory pattern of insulin release is disturbed in type 2 diabetes. Although sulfonylurea drugs are widely used for the treatment of this disease, their effect on insulin release patterns is not well established. The aim of the present study was to assess the impact of acute treatment and 5 weeks of sulfonylurea (gliclazide) treatment on insulin secretory dynamics in type 2 diabetic patients. To this end, 10 patients with type 2 diabetes (age 53 ؎ 2 years, BMI 27.5 ؎ 1.1 kg/m 2 , fasting plasma glucose 9.8 ؎ 0. ; placebo, 5.9 ؎ 0.9 vs. 7.2 ؎ 0.9 pmol ⅐ l -1 ⅐ pulse -1 , P ‫؍‬ 0.03; 5 weeks-elevated: gliclazide vs. placebo, 12.2 ؎ 2.5 vs. 9.4 ؎ 2.1 pmol ⅐ l -1 ⅐ pulse -1 , P ‫؍‬ 0.016). The frequency and regularity of insulin pulses were not modified significantly by the antidiabetic therapy. There was, however, a correlation between individual values for the acute improvement of regularity, as measured by ApEn, and the decrease in fasting plasma glucose during shortterm (5-week) gliclazide treatment (r ‫؍‬ 0.74, P ‫؍‬ 0.014, and r ‫؍‬ 0.77, P ‫؍‬ 0.009, for fine and coarse ApEn, respectively). In conclusion, the sulfonylurea agent gliclazide augments insulin secretion by concurrently increasing pulse mass and basal insulin secretion without changing secretory burst frequency or regularity. The data suggest a possible relationship between the improvement in short-term glycemic control and the acute improvement of regularity of the in vivo insulin release process.

Bedtime Administration of NN2211, a Long-Acting GLP-1 Derivative, Substantially Reduces Fasting and Postprandial Glycemia in Type 2 Diabetes

“…We found no change in baseline insulin release regularity as measured by ApEn. Previous studies of native GLP-1 and another insulin secretagogue, gliclazide, gave similar results, and it has been suggested that intervention in the early diabetic or prediabetic state is necessary to prevent the deterioration of baseline insulin release regularity (8,34). Deconvolution analysis of baseline insulin time series revealed no substantial changes in the distribution of basal versus pulsatile insulin release consistent with findings in previous studies in patients with type 2 diabetes (8,35).…”

Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes

“…Matthews et al [54] observed that elevated glucose increases the mass but not the frequency of plasma insulin bursts, and this has been confirmed in numerous studies ([55][56][57]). The action of glucose mainly to increase insulin pulse amplitude has also been observed in isolated human islets, where small numbers of islets could be perifused while insulin was sampled in their effluent [39].…”

“…Sulfonylureas, for example, which increase insulin secretion by closing KATP channels in the beta cell plasma membrane, acutely increase the amplitude, but not the frequency, of insulin pulse bursts or the basal insulin levels when studied in dogs [131], or in humans with T2DM [56]. An example of the modulation resulting from tolbutamide infusion is shown in Fig.…”

The use of gliclazide in the mirror of the individualized sulfonylurea therapy

“…E hatások valamennyi SU esetében alárendelt jelentő-ségűek és másodlagosak: minden valószínűség szerint a prandialis inzulinelválasztás első fázisának erősödésével és a pulzatilis inzulinszekréció helyreállásával vagy javulásával állnak összefüggésben [35].…”