Common Treatments for Diabetes Destroy the Pancreas and Leads to Worsening

A class of drugs called thiazolidinediones (TZDs), and specifically the brand name drug Avandia, were found to drastically increase the rate of heart attack. Given that 70% of diabetics already die of heart-related complications, an increase in this risk is devastating. The next punch came from an article in the September issue of Diabetes Research and Clinical Practice. Researchers confirmed earlier findings that another popular class of diabetic drugs, the sulfonylureas (such as brand name Glyburide), actually kill off the cells in the pancreas that make insulin, virtually ensuring that these patients will end up worsening and needing to inject insulin!!

Article from: http://www.sciencedirect.com/

Sulfonylurea and glinide reduce insulin content, functional expression of KATP channels, and accelerate apoptotic β-cell death in the chronic phase

Abstract

We previously found that chronic exposure to glibenclamide inhibits acute glibenclamide-induced insulin secretion by reducing the number of functional ATP-sensitive K+ (KATP) channels on the plasma membrane of pancreatic β-cells. In the present study, we compared sulfonylurea-induced and glinide-induced insulin secretion in pancreatic β-cells chronically exposed to these widely used oral hypoglycemic agents. Chronic exposure of pancreatic β-cells to sulfonylureas (glibenclamide or tolbutamide) and glinide (nateglinide) similarly impaired their acute effectiveness by reducing the insulin content and the number of functional KATP channels on the plasma membrane. Functional expression of the voltage-dependent Ca2+ channels (VDCCs), ion channels that play a critical role in the KATP channel dependent insulin secretory pathway, was similar to that in drug-untreated cells. Chronic exposure to each of the three agents similarly accelerated apoptotic β-cell death. Thus, reduction of the insulin content, reduction of the number of functional KATP channels on the plasma membrane, and acceleration of apoptotic β-cell death all are involved in impaired insulinotropic agent-induced acute insulin secretion in the chronic phase of sulfonylurea and glinide treatment. These findings help to clarify the mechanism of secondary failure after long-term therapy by these hypoglycemic agents, and should have important clinical implications regarding pharmacotherapy for type 2 diabetes.


Abbreviations: KATP, ATP-sensitive K+; VDCCs, voltage-dependent Ca2+ channels; DMEM, Dulbecco's modified Eagle's medium; KRBB, Krebs–Ringer bicarbonate buffer; RIA, radioimmunoassay; TUNEL, TdT-mediated dUTP nick end labeling; PBS, phosphate buffered saline; DMSO, dimethylsulfoxide

Akira Takahashia, b, Kazuaki Nagashimaa, , , Akihiro Hamasakia, Naomitsu Kuwamuraa, Yukiko Kawasakia, Hiroki Ikedaa, Yuichiro Yamadaa, Nobuya Inagakia, c and Yutaka Seinoa, d
aDepartment of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
bNakamura Hospital, Osaka, Japan
cCREST of Japan Science and Technology Cooperation (JST), Kyoto, Japan
dKansai Denryoku Hospital, Osaka, Japan