PMID- 22143007 OWN - NLM STAT- MEDLINE DCOM- 20150128 LR - 20181202 IS - 1938-2022 (Electronic) IS - 1938-2014 (Linking) VI - 4 IP - 1 DP - 2012 Jan-Feb TI - Overcoming the spatial barriers of the stimulus secretion cascade in pancreatic beta-cells. PG - 1-116 LID - 10.4161/isl.18338 [doi] AB - The ability of the pancreatic beta-cells to adapt the rate of insulin release in accordance to changes in circulating glucose levels is essential for glucose homeostasis. Two spatial barriers imposed by the plasma membrane and inner mitochondrial membrane need to be overcome in order to achieve stringent coupling between the different steps in the stimulus-secretion cascade. The first spatial barrier is overcome by the presence of a glucose transporter (GLUT) in the plasma membrane, whereas a low affinity hexokinase IV (glucokinase, GK) in the cytosol conveys glucose availability into a metabolic flux that triggers and accelerates insulin release. The mitochondrial inner membrane comprises a second spatial barrier that compartmentalizes glucose metabolism into glycolysis (cytosol) and tricarboxylate (TCA) cycle (mitochondrial matrix). The exchange of metabolites between cytosol and mitochondrial matrix is mediated via a set of mitochondrial carriers, including the aspartate-glutamate carrier (aralar1), alpha- ketoglutarate carrier (OGC), ATP/ADP carrier (AAC), glutamate carrier (GC1), dicarboxylate carrier (DIC) and citrate/isocitrate carrier (CIC). The scope of this review is to provide an overview of the role these carriers play in stimulus-secretion coupling and discuss the importance of these findings in the context of the exquisite glucose responsive state of the pancreatic beta-cell. FAU - Huypens, Peter R AU - Huypens PR AD - School of Pharmacy; Health Science Campus; University of Waterloo; Kitchener, CN Canada. FAU - Huang, Mei AU - Huang M AD - School of Pharmacy; Health Science Campus; University of Waterloo; Kitchener, CN Canada. FAU - Joseph, Jamie W AU - Joseph JW AD - School of Pharmacy; Health Science Campus; University of Waterloo; Kitchener, CN Canada. LA - eng PT - Journal Article PT - Review DEP - 20111206 PL - United States TA - Islets JT - Islets JID - 101495366 RN - 0 (Glucose Transport Proteins, Facilitative) RN - 0 (Mitochondrial Membrane Transport Proteins) RN - 146-91-8 (Guanosine Diphosphate) RN - 3KX376GY7L (Glutamic Acid) RN - 53-59-8 (NADP) RN - 86-01-1 (Guanosine Triphosphate) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Cell Membrane/*metabolism MH - Cytosol/metabolism MH - Glucose/*metabolism MH - Glucose Transport Proteins, Facilitative/*metabolism MH - Glutamic Acid/metabolism MH - Glycolysis MH - Guanosine Diphosphate/metabolism MH - Guanosine Triphosphate/metabolism MH - Humans MH - Insulin-Secreting Cells/*metabolism MH - Mitochondria/*metabolism MH - Mitochondrial Membrane Transport Proteins/*metabolism MH - Mitochondrial Membranes/metabolism MH - NADP/metabolism OTO - NOTNLM OT - carriers OT - insulin secretion OT - islets OT - metabolism OT - mitochondria EDAT- 2011/12/07 06:00 MHDA- 2015/01/30 06:00 CRDT- 2011/12/07 06:00 PHST- 2011/12/07 06:00 [entrez] PHST- 2011/12/07 06:00 [pubmed] PHST- 2015/01/30 06:00 [medline] AID - 18338 [pii] AID - 10.4161/isl.18338 [doi] PST - ppublish SO - Islets. 2012 Jan-Feb;4(1):1-116. doi: 10.4161/isl.18338. Epub 2011 Dec 6.