Applications of dipeptidyl peptidase IV inhibitors in diabetes mellitus.
A number of alternative therapies for type 2 diabetes are currently under development that take advantage of the actions of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide on the pancreatic beta-cell. One such approach is based on the inhibition of dipeptidyl peptidase IV (DP IV), the major enzyme responsible for degrading the incretins in vivo. DP IV exhibits characteristics that have allowed the development of specific inhibitors with proven efficacy in improving glucose tolerance in animal models of diabetes and type 2 human diabetics. While enhancement of insulin secretion, resulting from blockade of incretin degradation, has been proposed to be the major mode of inhibitor action, there is also evidence that inhibition of gastric emptying, reduction in glucagon secretion and important effects on beta-cell differentiation, mitogenesis and survival, by the incretins and other DP IV-sensitive peptides, can potentially preserve beta-cell mass, and improve insulin secretory function and glucose handling in diabetics.
McIntosh
Christopher H S
CH
University of British Columbia, Department of Cellular and Physiological Sciences, Vancouver, BC, Canada.
Demuth
Hans-Ulrich
HU
Kim
Su-Jin
SJ
Pospisilik
J Andrew
JA
Pederson
Raymond A
RA
D000595:Amino Acid Sequence; D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry / Q000378:metabolism*; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D011480:Protease Inhibitors / Q000627:therapeutic use*
D010446:Peptide Fragments; D011480:Protease Inhibitors; C101760:gastric inhibitory polypeptide (1-42); C055453:glucagon-like peptide 1 (7-36)amide; D005749:Gastric Inhibitory Polypeptide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D018819:Dipeptidyl Peptidase 4; D005947:Glucose