Nocturnal free fatty acids are uniquely elevated in the longitudinal development of diet-induced insulin resistance and hyperinsulinemia

2007 ◽  
Vol 292 (6) ◽  
pp. E1590-E1598 ◽  
Author(s):  
Stella P. Kim ◽  
Karyn J. Catalano ◽  
Isabel R. Hsu ◽  
Jenny D. Chiu ◽  
Joyce M. Richey ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Free Fatty Acids ◽  
Postprandial Glucose ◽  
High Fat ◽  
Glucose Levels ◽  
Dog Model ◽  
Fat Feeding ◽  
Hypercaloric Diet

Obesity is strongly associated with hyperinsulinemia and insulin resistance, both primary risk factors for type 2 diabetes. It has been thought that increased fasting free fatty acids (FFA) may be responsible for the development of insulin resistance during obesity, causing an increase in plasma glucose levels, which would then signal for compensatory hyperinsulinemia. But when obesity is induced by fat feeding in the dog model, there is development of insulin resistance and a marked increase in fasting insulin despite constant fasting FFA and glucose. We examined the 24-h plasma profiles of FFA, glucose, and other hormones to observe any potential longitudinal postprandial or nocturnal alterations that could lead to both insulin resistance and compensatory hyperinsulinemia induced by a high-fat diet in eight normal dogs. We found that after 6 wk of a high-fat, hypercaloric diet, there was development of significant insulin resistance and hyperinsulinemia as well as accumulation of both subcutaneous and visceral fat without a change in either fasting glucose or postprandial glucose. Moreover, although there was no change in fasting FFA, there was a highly significant increase in the nocturnal levels of FFA that occurred as a result of fat feeding. Thus enhanced nocturnal FFA, but not glucose, may be responsible for development of insulin resistance and fasting hyperinsulinemia in the fat-fed dog model.

From Obesity to Diabetes

2006 ◽  
Vol 76 (4) ◽  
pp. 172-177 ◽  
Author(s):  
Keller
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Free Fatty Acids ◽  
Vegetable Consumption ◽  
Prediabetic State ◽  
The Metabolic Syndrome ◽  
Life Style Changes

The prevalence of obesity has been increasing dramatically in the last decades in the whole world, not only in industrialized countries but also in developing areas. A major complication of obesity is insulin resistance and type 2 diabetes. Diabetes is also rapidly increasing world-wide – reaching a prevalence in adults of approx. 5–6% in Central Europe and in the US, and more than 50% in specific, genetically prone populations. This article reviews pathogenetic mechanisms linking obesity and type 2 diabetes. Emphasis is placed on the observation that excessive amounts of adipocytes are associated with an impairment of insulin sensitivity, a key feature of the "metabolic syndrome". This is a cluster of metabolic abnormalities such as type 2 diabetes, hypertension and dyslipidemia; all of them are enhanced by the presence of visceral (abdominal) obesity and all contribute to the increased cardiovascular risk observed in these patients. Besides release of free fatty acids, adipocytes secrete substances that contribute to peripheral insulin resistance, including adiponectin, resistin, TNF-α and interleukin 6. Increased turnover of free fatty acids interferes with intracellular metabolism of glucose in the muscle, and they exert lipotoxic effect on pancreatic β-cells. The pre-receptor metabolism of cortisol is enhanced in visceral adipose tissue by activation of 11 β-hydroxysteroid dehydrogenase type 1. A new class of anti-diabetic drugs (thiazolidinediones, or glitazones) bind to peroxisome proliferator activated receptor (PPAR-γ) and lower thereby plasma free fatty acids and cytokine production in adipocytes, in addition to a decrease of resistin and an increase in adiponectin observed in animals, resulting in an overall increase in insulin sensitivity and in an improvement of glucose homeostasis. However, the first step to avoid insulin resistance and prevent the development of diabetes should be a reduction in body weight in overweight subjecs, and an increase in physical activity. There are now three published randomized controlled trials demonstrating that in high risk individuals, life style changes with modest weight lost, associated with diminished fat intake and an increase in fruit and vegetable consumption result in marked inhibition of the transition from the prediabetic state to manifest type 2 diabetes.

Hyperinsulinemia, insulin resistance and free fatty acids. The dog model in diabetes and obesity research

2009 ◽  
Vol 105 (S 03) ◽  
pp. 39-39
Author(s):  
Adria Giacca ◽  
Stephanie Wiesenthal ◽  
Harmanjit Sandhu ◽  
Richard McCall ◽  
Vaja Tchipachvili ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Free Fatty Acids ◽  
Obesity Research ◽  
Dog Model ◽  
Diabetes And Obesity

scholarly journals Role of c-Jun N-terminal Kinase (JNK) in Obesity and Type 2 Diabetes

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 706 ◽  
Author(s):  
Justin Hou Ming Yung ◽  
Adria Giacca
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Free Fatty Acids ◽  
Chronic Inflammatory Disease ◽  
Low Grade ◽  
Global Epidemic ◽  
Progressive Development ◽  
Cell Dysfunction

Obesity has been described as a global epidemic and is a low-grade chronic inflammatory disease that arises as a consequence of energy imbalance. Obesity increases the risk of type 2 diabetes (T2D), by mechanisms that are not entirely clarified. Elevated circulating pro-inflammatory cytokines and free fatty acids (FFA) during obesity cause insulin resistance and ß-cell dysfunction, the two main features of T2D, which are both aggravated with the progressive development of hyperglycemia. The inflammatory kinase c-jun N-terminal kinase (JNK) responds to various cellular stress signals activated by cytokines, free fatty acids and hyperglycemia, and is a key mediator in the transition between obesity and T2D. Specifically, JNK mediates both insulin resistance and ß-cell dysfunction, and is therefore a potential target for T2D therapy.

scholarly journals Insulin resistance in type 2 diabetes youth relates to serum free fatty acids and muscle mitochondrial dysfunction

2017 ◽  
Vol 31 (1) ◽  
pp. 141-148 ◽  
Author(s):  
Melanie Cree-Green ◽  
Abhinav Gupta ◽  
Gregory V. Coe ◽  
Amy D. Baumgartner ◽  
Laura Pyle ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Free Fatty Acids ◽  
Mitochondrial Dysfunction ◽  
Serum Free Fatty Acids ◽  
Serum Free

scholarly journals Age and gender related differences in free fatty acid levels in patients with type 2 diabetes mellitus

2012 ◽  
Vol 2 (3) ◽  
pp. 184-191
Author(s):  
Šaćira Mandal ◽  
Adlija Čaušević ◽  
Maja Malenica ◽  
Šeherzada Hadžidedić ◽  
Besim Prnjavorac ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Type 2 Diabetes Mellitus ◽  
Free Fatty Acids ◽  
Diabetic Patients ◽  
Healthy Controls ◽  
Insulin Resistant ◽  
Glucose Levels

Introduction: Several decades of basic science and animal research provided considerable support for significant role of plasma free fatty acids (FFAs) in etiology of Type 2 diabetes mellitus (T2DM). Contradicting data related to signifi cance of elevated FFAs in plasma of patients with Type 2 diabetes prompted us to study concentrations of palmitic acid, stearic acid, and linoleic acid, in patients and healthy controls in an attempt to possibly use them as potential biomarkers in progression of the disease. Since aging is associated withincreased plasma glucose and insulin levels that are consistent with an insulin resistant state, in this study,age differences in the concentration of the above mentioned acids were tested.Methods: Progressive changes in their concentrations were followed through a period 6 months. All subjects included in the study were free of evidence of hepatitis B or C viral infection or active liver and kidney damage. Analysis of glucose and glycated hemoglobin levels were performed on BT PLUS 2000 analyzer using standard IFCC protocols, while concentrations of FFAs were analyzed by gas chromatography.Results: Our data demonstrated signifi cantly higher FFA values in plasma of diabetic patients as compared to healthy controls. There was a trend of correlation of FFAs levels with the blood glucose levels in diabetic patients, which was more prominent in diabetic men than in women.Conclusion: With aging, levels of free fatty acids signifi cantly increased in plasma of diabetic patients, and this effect was also more profound in male than in female diabetics.

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