Glibenclamide but not other sulphonylureas stimulates release of neuropeptide Y from perifused rat islets and hamster insulinoma cells

Abstract

We have studied the effects of first and second generation sulphonylureas on the release of insulin and neuropeptide tyrosine (NPY) from hamster insulinoma tumour (HIT-T15) cells and isolated rat islets. In the presence of 5·5 mmol/l glucose all sulphonylureas stimulated insulin release from the HIT cells (P<0·01 ANOVA, nd4) but only glibenclamide (GLIB, 10 µmol/l) stimulated the release of NPY (mean ... control 11·1 1·3 vs GLIB 28·4 4·1 fmol/h per 10 6 cells, P<0001, n=16). In isolated perifused rat islets both glibenclamide (10 µmol/l) (control 3·5 0·3 vs GLIB 6·3 0·2 fmol/min per islet, P<0·01, n=6) and tolbutamide (50 µmol/l) (control 4·7 0·1 vs TOLB 6·7 0·3 fmol/min per islet, P<0·01, n=6) enhanced glucose (8 mmol/l)-stimulated insulin release. However, only glibenclamide stimulated the release of NPY from the islets (control 3·4 0·8 vs GLIB 24·5 5 attomol/min per islet, P<0·01, n=6). Similar results were obtained in islets isolated from dexamethasonetreated rats. Glibenclamide treatment of HIT cells showed a prompt insulin release (10 min) while NPY secretion was slower (60 min), suggesting that internalization of the sulphonylurea is required to stimulate NPY release. Glibenclamide, the most common oral therapeutic agent in type 2 diabetes mellitus, is associated with release of the autocrine insulin secretion inhibitor, NPY.

In vivo assessment of antidiabetic and antioxidant activities of rosemary (Rosmarinus officinalis) in alloxan-diabetic rabbits

“…Similarly, it has been reported that chronic treatment with sulphonylureas such as glibenclamide leads to a decline in their insulin-tropic activity due to a seconder failure in increasing insulin secretion such as ␤-cell exhaustion or desensitisation to glucose (Kulkarni et al, 2000;Ball et al, 2004). In this study, the progressive reduction in the blood glucose levels of alloxan-diabetic rabbits might be due to a cumulative action of the extract during the period of treatment and also associated with an increase in the blood insulin levels.…”

Stevioside does not cause increased basal insulin secretion or β-cell desensitization as does the sulphonylurea, glibenclamide: Studies in vitro

“…*p < 0.05 and **p < 0.001 denotes significant differences from the corresponding control. and Filipponi et al, 1983;Kulkarni et al, 2000;Patane et al, 2000).…”

Prokineticin 2 Is a Hypothalamic Neuropeptide That Potently Inhibits Food Intake

“…Finally, the viability of the tissue was verified by a 45-min exposure to 56 mmol/l KCl. α-Melanocyte–stimulating hormone (α-MSH), cocaine and amphetamine–regulated transcript, thyrotropin-releasing hormone, corticotrophin-releasing hormone, neuropeptide Y, and agouti-related peptide (AgRP) in the aCSF were measured using established radioimmunoassay (22,30–34). …”