Regulation, perturbation, and correction of metabolic events in pancreatic islets.
The physiological regulation of nutrient catabolism in islet cells, its perturbation in non-insulin-dependent diabetes mellitus, and the tools available to compensate for such a perturbation are reviewed. In terms of physiology, emphasis is placed on the relevance of glucokinase to hexose-induced insulin release, protein-to-protein interaction and enzyme-to-enzyme channelling, and the preferential stimulation of mitochondrial oxidative events in glucose-stimulated B-cells. In terms of pathology, attention is drawn to the deficiency of FAD-linked mitochondrial glycerophosphate dehydrogenase. Last, as far as therapeutic aspects are concerned, the potential usefulness of hypoglycemic sulfonylureas and meglitinide analogs, adenosine analogs, non-glucidic nutrients, and GLP-1 is underlined.
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
W J
WJ
Malaisse
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D005934:Glucagon / Q000494:pharmacology / Q000627:therapeutic use; D052216:Glucagon-Like Peptide 1; D005941:Glucokinase / Q000378:metabolism; D005993:Glycerolphosphate Dehydrogenase / Q000172:deficiency / Q000378:metabolism; D006601:Hexoses / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use; D011498:Protein Precursors / Q000494:pharmacology / Q000627:therapeutic use; D013453:Sulfonylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use
D006601:Hexoses; D007004:Hypoglycemic Agents; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D013453:Sulfonylurea Compounds; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005993:Glycerolphosphate Dehydrogenase; D005941:Glucokinase; D000241:Adenosine