Oral Insulin Supplementation Attenuates Atherosclerosis Progression in Apolipoprotein E-Deficient Mice

Shamir, Raanan; Shehadeh, Naim; Eshach-Adiv, Orly; Coleman, Raymond; Kaplan, Marielle; Hamoud, Shadi; Lischinsky, Sophie; Hayek, Tony

doi:10.1161/01.atv.0000042232.42883.56

Cited by 57 publications

(43 citation statements)

References 41 publications

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“…4 Insulin also inhibits the development of atherosclerosis in apolipoprotein E-knockout mice, which develop atherosclerosis spontaneously. 30 These observations are consistent with the myocardial protective effects suggested by our study.…”

Section: Discussionsupporting

confidence: 93%

Anti-Inflammatory and Profibrinolytic Effect of Insulin in Acute ST-Segment–Elevation Myocardial Infarction

et al. 2004

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Background-The clinical benefits of insulin previously observed in acute ST-segment-elevation myocardial infarction (STEMI) may be partially explained by an anti-inflammatory effect. We assessed this potential effect of insulin in STEMI patients treated with fibrinolytics. Methods and Results-Thirty-two patients receiving reteplase were randomly assigned infusions of either insulin at 2.5 U/h, dextrose, and potassium (GIK) or normal saline and potassium (C) for 48 hours. Plasma concentrations of high-sensitivity C-reactive protein (CRP), serum amyloid A (SAA), plasminogen activator inhibitor-1 (PAI-1), creatine kinase (CK), and CK-MB were measured at baseline and sequentially for 48 hours. Total p47 phox protein in mononuclear cells was measured in a subgroup of 13 subjects. Baseline CRP and SAA were significantly increased (2-to 4-fold) at 24 and 48 hours in each group (PϽ0.01). However, in the insulin group, there was a significant (PϽ0.05) attenuation of the absolute rise in concentration of CRP and SAA from baseline. The absolute increase of CRP and SAA was reduced by 40% (CRP) and 50% (SAA) at 24 hours and at 48 hours compared with the control group. The absolute increase in PAI-1 from baseline and the percentage increase in p47 phox over 48 hours were significantly (PϽ0.05) lower in the insulin-treated group. CK-MB peaked earlier and tended to be lower in insulin-treated subjects, especially in patients with inferior MI. Conclusions-Insulin

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Section: Discussionsupporting

confidence: 93%

Anti-Inflammatory and Profibrinolytic Effect of Insulin in Acute ST-Segment–Elevation Myocardial Infarction

et al. 2004

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“…7 (July 2005) in mice (9,10). Furthermore, we have demonstrated that oral insulin supplementation attenuates the atherosclerotic process in apoE-deficient mice (11). However, in neither study were the effects of oral insulin supplementation on intestinal parameters beyond the suckling period explored.…”

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confidence: 88%

Intestinal and Systemic Effects of Oral Insulin Supplementation in Rats After Weaning

et al. 2005

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Oral insulin has intestinal trophic effects in suckling animals. In mice, lower glucose and lipid levels may be seen when oral insulin is given after the weaning period. The purpose of the present study is to examine local and systemic effects of oral insulin supplementation in rats in the postweaning period. Immediately after weaning, Sprague-Dawley rats received either drinking water (controls) or oral insulin in their drinking water (1 U/ml) for either 1 week or 6 weeks. Intestinal mucosal parameters (bowel and mucosal weight, mucosal DNA and protein) and histological changes were examined in all study groups. Glucose levels were monitored weekly, and at the end of the study, blood levels of glucose, lipids, and insulin were measured in the fasting state. After 1 week of insulin supplementation, mucosal weight in duodenum and jejunum as well as jejunal DNA content were significantly higher in insulin-supplemented rats compared to controls. Duodenal circumference and villus height in jejunum were significantly higher in insulin-supplemented rats compared to controls on both day 7 and day 42. Total cholesterol levels were significantly lower in the study group compared with the controls. We conclude that oral insulin supplementation exerts intestinal trophic effects, as well as systemic effects in the postweaning period in rats.

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“…Clearly, insulin has a direct inhibitory effect on endotoxin induced inflammation. More recently animal studies have shown that in apo E deleted mice, the usual development of atherosclerosis is reduced by insulin administration [30]. Furthermore, an interference with insulin signal transduction leads to atherogenesis as is observed in IRS-2 deleted mouse [31].…”

Section: Anti-inflammatory and Cardioprotective Effects Of Insulin Inmentioning

confidence: 98%

Use of Insulin to Improve Glycemic Control in Diabetes Mellitus

Dandona

Chaudhuri

Ghanim

et al. 2008

Cardiovasc Drugs Ther

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These findings are of great interest as it is possible that the prevention of macrovascular complications in type 2 diabetes may require the use of those glucose lowering drugs which have additional anti-inflammatory effects in addition to the control of comorbid conditions (hypertension and dyslipidemia) associated with this disease. Results of future clinical trials are awaited to confirm the benefits of this approach in the primary and secondary prevention of macrovascular complications in type 2 diabetes.

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Oral Insulin Supplementation Attenuates Atherosclerosis Progression in Apolipoprotein E-Deficient Mice

Cited by 57 publications

References 41 publications

Anti-Inflammatory and Profibrinolytic Effect of Insulin in Acute ST-Segment–Elevation Myocardial Infarction

Anti-Inflammatory and Profibrinolytic Effect of Insulin in Acute ST-Segment–Elevation Myocardial Infarction

Intestinal and Systemic Effects of Oral Insulin Supplementation in Rats After Weaning

Use of Insulin to Improve Glycemic Control in Diabetes Mellitus

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