Mechanisms linking obesity to insulin resistance and type 2 diabetes

@article{Kahn2006MechanismsLO,
  title={Mechanisms linking obesity to insulin resistance and type 2 diabetes},
  author={Steven E. Kahn and Rebecca L. Hull and Kristina M. Utzschneider},
  journal={Nature},
  year={2006},
  volume={444},
  pages={840-846}
}
Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes. In obese individuals, adipose tissue releases increased amounts of non-esterified fatty acids, glycerol, hormones, pro-inflammatory cytokines and other factors that are involved in the development of insulin resistance. When insulin resistance is accompanied by dysfunction of pancreatic islet β-cells — the cells that release insulin — failure to control blood glucose levels results. Abnormalities… 

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References

SHOWING 1-10 OF 95 REFERENCES

Role of Fatty Acids in the Pathogenesis of Insulin Resistance and NIDDM

Continuously elevated levels of plasma FFAs may play a key role in the pathogenesis of NIDDM in predisposed individuals by impairing peripheral glucose utilization and by promoting hepatic glucose overproduction.

Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome.

The pathophysiology of adiponectin and adiponECTin receptors in insulin resistance, diabetes, and the metabolic syndrome is described and potential versatile therapeutic targets to combat obesity-linked diseases characterized by insulin resistance are described.

The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes

  • S. Kahn
  • Medicine, Biology
    Diabetologia
  • 2003
Greater understanding of the relative roles of insulin resistance and beta-cell dysfunction in Type 2 diabetes can anticipate advances in the identification of genes contributing to the development of the disease as well as approaches to the treatment and prevention of Type 1 diabetes.

Primacy of hepatic insulin resistance in the development of the metabolic syndrome induced by an isocaloric moderate-fat diet in the dog.

The results indicate that a diet enriched with a moderate amount of fat results in the development of both subcutaneous and visceral adiposity, hyperinsulinemia, and a modest degree of peripheral insulin resistance.

Inflammation and insulin resistance.

This Is the second of two articles describing a symposium on the relationship between inflammation and insulin resistance that was held in Niagra Falls, NY, 20–21 September 2002. Antonio Ceriello

Preventing diabetes--applying pathophysiological and epidemiological evidence.

This is a review of research carried out in Japanese Americans that points towards possible approaches to prevention of type 2 diabetes mellitus and shows that the abnormalities that characterize the metabolic syndrome play a significant role.

Type 2 Diabetes-a Matter of ß-Cell Life and Death?

Evidence supporting the notion that increased β-cell apoptosis is an important factor contributing toβ-cell loss and the onset of type 2 diabetes is discussed.

Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.

It is proposed that obesity-related insulin resistance is, at least in part, a chronic inflammatory disease initiated in adipose tissue, and that macrophage-related inflammatory activities may contribute to the pathogenesis of obesity-induced insulin resistance.

Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes

It is shown that expression of retinol binding protein-4 (RBP4) is elevated in adipose tissue of adipose-Glut4-/- mice and RBP4 is an adipocyte-derived ‘signal’ that may contribute to the pathogenesis of type 2 diabetes.

Role of Insulin Resistance in Human Disease

The possibility is raised that resistance to insulin-stimulated glucose uptake and hyperinsulinemia are involved in the etiology and clinical course of three major related diseases— NIDDM, hypertension, and CAD.
...