Modulation of cyclic nucleotides and cyclic nucleotide phosphodiesterases in pancreatic islet beta-cells and intestinal L-cells as targets for treating diabetes mellitus.
Cyclic 3'5'-AMP (cAMP) is an important physiological amplifier of glucose-induced insulin secretion by the pancreatic islet beta-cell. In the beta-cell, cAMP is formed by the activity of adenylyl cyclase, especially in response to the incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic peptide. cAMP may also play a similar role in regulating GLP-1 secretion from intestinal L-cells. cAMP influences many steps involved in glucose-induced insulin secretion and may be important in regulating pancreatic islet beta-cell differentiation, growth and survival. cAMP itself is rapidly degraded in the pancreatic islet beta-cell by cyclic nucleotide phosphodiesterase enzymes. This review will discuss the possibility of targeting cAMP mechanisms in the treatment of type 2 diabetes mellitus, in which insulin release in response to glucose is impaired.
Furman
Brian
B
University of Strathclyde, Strathclyde Institute of Pharmacy and Biomedical Sciences, Taylor Street, Glasgow G4 0NR, UK. b.l.furman@strath.ac.uk
Pyne
Nigel
N
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000502:physiology*; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use
D010726:Phosphodiesterase Inhibitors; D011480:Protease Inhibitors; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D000242:Cyclic AMP; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D018819:Dipeptidyl Peptidase 4; D006152:Cyclic GMP