Cardiovascular Disease in the Insulin-Resistant, Atherosclerosis-Prone JCR :LA-cp Rat

2013 ◽  
pp. 73-86
Keyword(s):  
Cardiovascular Disease ◽  
Insulin Resistant

Pioglitazone administration decreases cardiovascular disease risk factors in insulin-resistant smokers

Metabolism ◽  
2008 ◽  
Vol 57 (8) ◽  
pp. 1108-1114 ◽  
Author(s):  
Fahim Abbasi ◽  
Helke M.F. Farin ◽  
Cindy Lamendola ◽  
Leigh McGraw ◽  
Tracey McLaughlin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Cardiovascular Disease Risk Factors ◽  
Insulin Resistant

scholarly journals Cardiac Development and Transcription Factors: Insulin Signalling, Insulin Resistance, and Intrauterine Nutritional Programming of Cardiovascular Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Annelene Govindsamy ◽  
Strinivasen Naidoo ◽  
Marlon E. Cerf
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Transcription Factors ◽  
Cardiac Development ◽  
Insulin Signalling ◽  
Life Stages ◽  
Sequential Process ◽  
Insulin Resistant ◽  
Sensitive Organ ◽  
And Function

Programming with an insult or stimulus during critical developmental life stages shapes metabolic disease through divergent mechanisms. Cardiovascular disease increasingly contributes to global morbidity and mortality, and the heart as an insulin-sensitive organ may become insulin resistant, which manifests as micro- and/or macrovascular complications due to diabetic complications. Cardiogenesis is a sequential process during which the heart develops into a mature organ and is regulated by several cardiac-specific transcription factors. Disrupted cardiac insulin signalling contributes to cardiac insulin resistance. Intrauterine under- or overnutrition alters offspring cardiac structure and function, notably cardiac hypertrophy, systolic and diastolic dysfunction, and hypertension that precede the onset of cardiovascular disease. Optimal intrauterine nutrition and oxygen saturation are required for normal cardiac development in offspring and the maintenance of their cardiovascular physiology.

scholarly journals Empagliflozin Restores Cardiac Metabolic Flexibility in Diet-induced Obese C57BL6/J Mice

2021 ◽  
Author(s):  
Bingxian Xie ◽  
Wesley Ramirez ◽  
Amanda M. Mills ◽  
Brydie R. Huckestein ◽  
Moira Anderson ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cardiac Hypertrophy ◽  
Sglt2 Inhibitor ◽  
Inhibitor Therapy ◽  
Metabolic Flexibility ◽  
Protective Effects ◽  
Insulin Resistant ◽  
Ischemic Stress

Abstract BackgroundSodium-glucose co-transporter type 2 (SGLT2) inhibitor therapy to treat type 2 diabetes unexpectedly reduced all-cause mortality and hospitalization due to heart failure in several large-scale clinical trials, and has since been shown to produce similar cardiovascular disease-protective effects in patients without diabetes. How SGLT2 inhibitor therapy improves cardiovascular disease outcomes remains incompletely understood. Metabolic flexibility refers to the ability of a cell or organ to adjust its use of metabolic substrates, such as glucose or fatty acids, in response to physiological or pathophysiological conditions, and is a feature of a healthy heart that may be lost during diabetic cardiomyopathy and in the failing heart. While several studies have addressed metabolic changes in hearts in response to SGLT2 inhibitor therapy, none have specifically assessed metabolic flexibility in an in vivo system. We therefore undertook the described studies to determine the effects of SGLT2 inhibitor therapy on cardiac metabolic flexibility in vivo in obese, insulin resistant mice.MethodsDiet-induced obese mice were treated with the SGLT2 inhibitor empagliflozin (EMPA; 10 mg/kg/d) for four weeks prior to study and compared with untreated obese and lean controls. We assessed changes in body weight and composition, plasma metabolites in response to fasting/re-feeding, cardiac hypertrophy by echocardiography, the response to ischemic stress following coronary artery ligation, as well as cardiac-specific rates of relative glucose and fatty acid utilization using a [U13C]-glucose infusion during fasting and hyperinsulinemic euglycemic clamp.ResultsEMPA-treated mice presented with reduced cardiac hypertrophy and protection from ischemic stress compared with obese controls. In the fasted state, relative rates of cardiac glucose and fatty acid utilization were similar in control and EMPA-treated mice. During the hyperinsulinemic euglycemic clamp, rates of cardiac glucose utilization and metabolic flexibility were reduced in obese compared with lean mice, and EMPA-treatment partially restored both features. ConclusionsSGLT2 inhibitor therapy restored cardiac metabolic flexibility in obese, insulin resistant mice, and was associated with reduced cardiac hypertrophy and protection from ischemia. These observations suggest that the cardiovascular disease-protective effects of SGLT2 inhibitors may in part be explained by beneficial effects on cardiac metabolic substrate selection.

Is There a Simple Way to Identify Insulin-Resistant Individuals at Increased Risk of Cardiovascular Disease?

2005 ◽  
Vol 96 (3) ◽  
pp. 399-404 ◽  
Author(s):  
Tracey McLaughlin ◽  
Gerald Reaven ◽  
Fahim Abbasi ◽  
Cindy Lamendola ◽  
Mohammed Saad ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Insulin Resistant ◽  
Increased Risk

Physical activity, fitness and cardiovascular disease risk in adults: interactions with insulin resistance and obesity

2006 ◽  
Vol 110 (4) ◽  
pp. 409-425 ◽  
Author(s):  
Jason M. R. Gill ◽  
Dalia Malkova
Keyword(s):  
Physical Activity ◽  
Cardiovascular Disease ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Normal Weight ◽  
Metabolic Dysfunction ◽  
Cvd Risk ◽  
Insulin Resistant ◽  
The Metabolic Syndrome ◽  
High Level

There is a considerable body of evidence gathered from studies over the past half a century indicating that a high level of physical activity and a moderately high or high degree of cardiorespiratory fitness reduces the risk of CVD (cardiovascular disease). Recent data suggest that high levels of physical activity or fitness may be particularly beneficial to individuals with insulin-resistant conditions, such as the metabolic syndrome, Type II diabetes or obesity. These individuals, if unfit and sedentary, exhibit increased CVD risk, but their dose–response relationship for physical activity/fitness appears to be particularly steep such that, when they undertake high levels of activity (or have high fitness), their level of risk becomes closer to that of their normal weight or nondiabetic peers. This may be due to effects of physical activity in normalizing the metabolic dysfunction particularly associated with insulin-resistant conditions.

scholarly journals Pair feeding-mediated changes in metabolism: stress response and pathophysiology in insulin-resistant, atherosclerosis-prone JCR:LA-cp rats

2008 ◽  
Vol 294 (6) ◽  
pp. E1078-E1087 ◽  
Author(s):  
James C. Russell ◽  
Spencer D. Proctor ◽  
Sandra E. Kelly ◽  
David N. Brindley
Keyword(s):  
Cardiovascular Disease ◽  
Animal Model ◽  
Macrovascular Disease ◽  
Acid Oxidation ◽  
Human Beings ◽  
Nonesterified Fatty Acids ◽  
Insulin Resistant ◽  
The Metabolic Syndrome ◽  
End Stage ◽  
Myocardial Lesions

Rats of the JCR:LA-cp strain, which are homozygous for the cp gene ( cp/ cp), are obese, insulin-resistant, and hyperinsulinemic. They exhibit associated micro- and macrovascular disease and end-stage ischemic myocardial lesions and are highly stress sensitive. We subjected male cp/ cp rats to pair feeding (providing the rats each day with the amount of food eaten by matched freely fed animals), a procedure that alters the diurnal feeding pattern, leading to a state of intermittent caloric restriction. Effects on insulin, glucose, and lipid metabolism, response to restraint stress, aortic contractile/relaxant response, and myocardial lesion frequency were investigated. Pair-fed young (12-wk-old) cp/ cp rats had lower insulin and glucose levels (basal and following restraint), consistent with increased insulin sensitivity, but a greater increase in plasma nonesterified fatty acids in response to restraint. These effects were unrelated to lipolytic rates in adipose tissue but may be related to reduced fatty acid oxidation in skeletal muscle. Older (24-wk-old) pair-fed cp/ cp rats had significantly reduced plasma triglyceride levels, improved micro- and macrovascular function, and reduced severity of ischemic myocardial lesions. These changes indicate a significant amelioration of end-stage disease processes in this animal model and the complexity of metabolic/physiological responses in studies involving alterations in food intake. The effects illustrate the sensitivity of the JCR:LA-cp rat, an animal model for the metabolic syndrome and associated cardiovascular disease, to the environmental and experimental milieu. Similar stress-related mechanisms may play a role in metabolically induced cardiovascular disease in susceptible human beings.

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