PMID- 17257271
OWN - NLM
STAT- MEDLINE
DCOM- 20070629
LR  - 20071115
IS  - 0742-3071 (Print)
IS  - 0742-3071 (Linking)
VI  - 24
IP  - 2
DP  - 2007 Feb
TI  - Mechanisms of protective effects induced by blockade of the renin-angiotensin 
      system: novel role of the pancreatic islet angiotensin-generating system in Type 
      2 diabetes.
PG  - 110-6
AB  - Large clinical trials have shown that inhibition of the renin-angiotensin system 
      (RAS) can delay and/or prevent the onset of Type 2 diabetes mellitus (T2DM) in 
      high-risk individuals, such as those with hypertension or chronic heart failure. 
      Moreover, a meta-analysis of these randomized clinical studies concluded that the 
      mean weighted relative risk of development of T2DM was reduced by 25% in those 
      patients treated with angiotensin II receptor blockers or angiotensin-converting 
      enzyme inhibitors. In spite of these firm clinical data, the mechanistic pathways 
      mediating the protective activity of RAS blockade have yet to be resolved. Of 
      particular interest is the recently identified local pancreatic RAS and, perhaps 
      more importantly, the finding that it is up-regulated in animal models of T2DM. 
      This putative local RAS may regulate pancreatic islet blood flow, oxygen tension, 
      and islet (pro)insulin biosynthesis. It might also mediate the generation of 
      reactive oxygen species, thereby causing oxidative stress-induced pancreatic 
      beta-cell apoptosis and fibrosis. Moreover, findings that RAS blockade improved 
      beta-cell secretory function and cell mass in experimental animal models of Type 
      2 diabetes indicate that inhibition of RAS activation may play a pivotal role in 
      protecting islet cell function, and furthermore may prevent the development of 
      overt T2DM. Such data supporting the involvement of the local pancreatic RAS in 
      islet function, as well as a causal relationship between RAS activation and T2DM, 
      and RAS induced beta-cell dysfunction, mandate further investigation into the 
      role of RAS in the pathogenesis of the progressive islet impairment observed in 
      patients with T2DM.
FAU - Leung, P S
AU  - Leung PS
AD  - Department of Physiology, Faculty of Medicine, The Chinese University of Hong 
      Kong, Shatin, Hong Kong. psleung@cuhk.edu.hk
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Diabet Med
JT  - Diabetic medicine : a journal of the British Diabetic Association
JID - 8500858
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Vasoconstrictor Agents)
RN  - 11128-99-7 (Angiotensin II)
SB  - IM
MH  - Angiotensin II
MH  - Angiotensin-Converting Enzyme Inhibitors/*therapeutic use
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Heart Failure/prevention & control
MH  - Humans
MH  - Hypertension/prevention & control
MH  - Insulin Resistance/physiology
MH  - Islets of Langerhans/*drug effects
MH  - Renin-Angiotensin System/*drug effects
MH  - Vasoconstrictor Agents/*therapeutic use
RF  - 63
EDAT- 2007/01/30 09:00
MHDA- 2007/06/30 09:00
CRDT- 2007/01/30 09:00
PHST- 2007/01/30 09:00 [pubmed]
PHST- 2007/06/30 09:00 [medline]
PHST- 2007/01/30 09:00 [entrez]
AID - DME2072 [pii]
AID - 10.1111/j.1464-5491.2007.02072.x [doi]
PST - ppublish
SO  - Diabet Med. 2007 Feb;24(2):110-6. doi: 10.1111/j.1464-5491.2007.02072.x.