Biomaterial Database

Direct inhibition of the pancreatic beta-cell ATP-regulated potassium channel by alpha-ketoisocaproate. 1998

R Bränström, and S Efendić, and P O Berggren, and O Larsson

Rolf Luft Center for Diabetes Research, Department of Molecular Medicine, Karolinska Institute, S-171 76 Stockholm, Sweden.

The ATP-regulated potassium (KATP) channel plays an essential role in the control of insulin release from the pancreatic beta-cell. In the present study we have used the patch-clamp technique to study the direct effects of alpha-ketoisocaproate on the KATP channel in isolated patches and intact pancreatic beta-cells. In excised inside-out patches, the activity of the KATP channel was dose-dependently inhibited by alpha-ketoisocaproate, half-maximal concentration being approximately 8 mM. The blocking effect of alpha-ketoisocaproate was fully reversible. Stimulation of channel activity by the addition of ATP/ADP (ratio 1) did not counteract the inhibitory effect of alpha-ketoisocaproate. In the presence of the metabolic inhibitor sodium azide, alpha-ketoisocaproate was still able to inhibit single channel activity in excised patches and to block whole cell KATP currents in intact cells. No effect of alpha-ketoisocaproate could be obtained on either the large or the small conductance Ca2+-regulated K+ channel. Enzymatic treatment of the patches with trypsin prevented the inhibitory effect of alpha-ketoisocaproate. Based on these observations, it is unlikely that the blocking effect of alpha-ketoisocaproate is due to an unspecific effect on K+ channel pores. Leucine, the precursor of alpha-ketoisocaproate, did not affect KATP channel activity in excised patches. Our findings are compatible with the view that alpha-ketoisocaproate not only affects the beta-cell stimulus secretion coupling by generation of ATP but also by direct inhibition of the KATP channel.

UI	MeSH Term	Description	Entries
D007515	Islets of Langerhans	Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.	Islands of Langerhans,Islet Cells,Nesidioblasts,Pancreas, Endocrine,Pancreatic Islets,Cell, Islet,Cells, Islet,Endocrine Pancreas,Islet Cell,Islet, Pancreatic,Islets, Pancreatic,Langerhans Islands,Langerhans Islets,Nesidioblast,Pancreatic Islet
D007651	Keto Acids	Carboxylic acids that contain a KETONE group.	Oxo Acids,Oxoacids,Acids, Keto,Acids, Oxo
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008297	Male		Males
D008820	Mice, Obese	Mutant mice exhibiting a marked obesity coupled with overeating, hyperglycemia, hyperinsulinemia, marked insulin resistance, and infertility when in a homozygous state. They may be inbred or hybrid.	Hyperglycemic Mice,Obese Mice,Mouse, Hyperglycemic,Mouse, Obese,Hyperglycemic Mouse,Mice, Hyperglycemic,Obese Mouse
D004594	Electrophysiology	The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D005260	Female		Females
D000255	Adenosine Triphosphate	An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.	ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014357	Trypsin	A serine endopeptidase that is formed from TRYPSINOGEN in the pancreas. It is converted into its active form by ENTEROPEPTIDASE in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4.	Tripcellim,Trypure,beta-Trypsin,beta Trypsin