The glucagon-like peptide-1 analogue exendin-4 reverses impaired intracellular Ca(2+) signalling in steatotic hepatocytes.

摘要: The release of Ca(2+) from the endoplasmic reticulum (ER) and subsequent replenishment ER by entry through store-operated channels (SOCE) play critical roles in regulation liver metabolism adrenaline, glucagon other hormones. Both are severely inhibited steatotic hepatocytes. Exendin-4, a slowly-metabolised glucagon-like peptide-1 (GLP-1) analogue, is known to reduce glucose output lipid, but mechanisms involved not well understood. aim this study was determine whether exendin-4 alters intracellular homeostasis hepatocytes, evaluate involved. Exendin-4 completely reversed lipid-induced inhibition SOCE cells, did reverse release. action on rapid onset mimicked GLP-1 or dibutyryl cyclic AMP. In caused decrease lipid (half time 6.5min), accumulation cells incubated presence palmitate plus inhibitor BTP-2, enhanced formation Hormone-stimulated extracellular glycogen replete compared that non-steatotic effect exendin-4. It concluded that, reverses leading restoration hormone-regulated cytoplasmic signalling. mechanism may involve receptors, AMP, lipolysis, decreased diacylglycerol activity protein kinase C.