PMID- 21293084
OWN - NLM
STAT- MEDLINE
DCOM- 20110322
LR  - 20181201
IS  - 1941-9260 (Electronic)
IS  - 0032-5481 (Linking)
VI  - 123
IP  - 1
DP  - 2011 Jan
TI  - Focus on incretin-based therapies: targeting the core defects of type 2 diabetes.
PG  - 53-65
LID - 10.3810/pgm.2011.01.2245 [doi]
AB  - Glucose homeostasis is regulated by a complex interaction of hormones, 
      principally including insulin, glucagon, amylin, and the incretins. Glucagon, 
      cortisol, catecholamines, and growth hormone serve as the classic glucose 
      counterregulatory hormones. The incretins are hormones released by 
      enteroendocrine cells in the intestine in response to a meal. Classically, type 2 
      diabetes mellitus (T2DM) has been considered to be a triad of insulin resistance, 
      increased hepatic gluconeogenesis, and progressive beta-cell exhaustion/failure. 
      However, disordered enteroendocrine physiology, specifically the reduced activity 
      of glucagon-like peptide-1 (GLP-1), is also a principal pathophysiologic 
      abnormality of the disease. Glucagon-like peptide-1 receptor agonists that have 
      been studied include exenatide and liraglutide, which have been approved by the 
      US Food and Drug Administration for use in patients with T2DM. Sitagliptin and 
      saxagliptin, both approved for use in the United States, modulate incretin 
      physiology by inhibiting degradation of GLP-1 by the enzyme dipeptidyl 
      peptidase-4 (DPP-4). Modulators of incretin physiology have been shown to improve 
      glycemic control with a low risk for hypoglycemia and beneficially affect beta-cell 
      function. Unlike the DPP-4 inhibitors, GLP-1 receptor agonist therapy also 
      produces weight loss, an important consideration given the close association 
      among T2DM, overweight/obesity, and cardiovascular disease. The GLP-1 receptor 
      agonists have also demonstrated beneficial effects on cardiovascular risk factors 
      other than hyperglycemia and excess body weight, such as lipid concentrations and 
      blood pressure. This article describes incretin physiology and studies of 
      pharmacologic therapy designed to address the blunted incretin response in 
      patients with T2DM. Information was obtained by a search of the PubMed and 
      MEDLINE databases for articles published from January 1, 1995 to June 1, 2009.
FAU - Jellinger, Paul S
AU  - Jellinger PS
AD  - University of Miami, Miami, FL, USA. pjellinger@diabetes-endocare.com
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Postgrad Med
JT  - Postgraduate medicine
JID - 0401147
RN  - 0 (Dipeptides)
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (GLP1R protein, human)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Incretins)
RN  - 0 (Peptides)
RN  - 0 (Pyrazines)
RN  - 0 (Receptors, Glucagon)
RN  - 0 (Triazoles)
RN  - 0 (Venoms)
RN  - 839I73S42A (Liraglutide)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - 9GB927LAJW (saxagliptin)
RN  - 9P1872D4OL (Exenatide)
RN  - PJY633525U (Adamantane)
RN  - TS63EW8X6F (Sitagliptin Phosphate)
SB  - IM
MH  - Adamantane/analogs & derivatives/therapeutic use
MH  - Cardiovascular Diseases/prevention & control
MH  - Clinical Trials as Topic
MH  - Diabetes Mellitus, Type 2/*drug therapy/metabolism/physiopathology
MH  - Dipeptides/therapeutic use
MH  - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
MH  - Exenatide
MH  - Glucagon-Like Peptide 1/analogs & derivatives/*metabolism/therapeutic use
MH  - Glucagon-Like Peptide-1 Receptor
MH  - Humans
MH  - Hypoglycemic Agents/*therapeutic use
MH  - Incretins/*therapeutic use
MH  - Liraglutide
MH  - Peptides/therapeutic use
MH  - Pyrazines/therapeutic use
MH  - Receptors, Glucagon/*agonists
MH  - Sitagliptin Phosphate
MH  - Triazoles/therapeutic use
MH  - Venoms/therapeutic use
EDAT- 2011/02/05 06:00
MHDA- 2011/03/23 06:00
CRDT- 2011/02/05 06:00
PHST- 2011/02/05 06:00 [entrez]
PHST- 2011/02/05 06:00 [pubmed]
PHST- 2011/03/23 06:00 [medline]
AID - 10.3810/pgm.2011.01.2245 [doi]
PST - ppublish
SO  - Postgrad Med. 2011 Jan;123(1):53-65. doi: 10.3810/pgm.2011.01.2245.