Myocardial Insulin Signaling and Glucose

There were almost 200 million people suffering from diabetes mellitus all over the world. This number was expected be as high as 48.3 million by 2050 in America 1. The total cost of diabetes mellitus was estimated to be $149 billion and will reach as high as $192 billion by 2020 2. Moreover, as a long-term complication of type 2 diabetes mellitus, cardiovascular disease was the leading cause of death in diabetic patients. Patients with type 2 diabetic suffered from increasing risk of congestive heart failure and higher mortality rate due to myocardial infarction 3. Type 2 diabetes is so prevalent, expensive, and lethal that it becomes a worldwide concerning disease. However, the mechanisms and best treatment are still needed to be discerned.

Bariatric surgery, like ileal transposition (IT), have been documented to improve glucose homeostasis and lead to improvement in glycemic control, resulting from caloric restriction and alternations in the gut hormones that control insulin secretion 4. The concept of ileal interposition was first described in rodent experiments 5. It has been confirmed that ileal transposition can improve glucose tolerance compared with other bariatric surgeries, was faster to perform and yielded a shorter recovery time in animal models of type 2 diabetes 6, 7. The potential mechanism for this may include weight reduction, food restriction, bypassing of the proximal small intestine, and early food exposure to distal small intestine. Besides, glucagon-like peptide-1(GLP-1), as a potent insulin secretagogue, is secreted by the L cells of the distal ileum in response to the ingested nutrients, and secreted more in IT. These indicate that IT may act more powerful on reversal of type 2 diabetes as well as the insulin signaling pathway than other bariatric surgeries.

Bariatric surgery has been shown to improve left ventricular systolic dysfunction in young morbidly obese individuals with non-ischemic cardiomyopathy. The alternations in the insulin response and reduced direct toxic effects of adiposity on cardiomyocytes may contribute to myocardial function improvement. Also, partial regression of cardiac hypertrophy and reversal of both diastolic dysfunction and aortic distensibility impairment were found 1 year after bariatric surgery 8.

The process of autophosphorylation of a number of tyrosine residues can be initiated by binding of insulin to the insulin receptor 9. These tyrosine residues could be recognised by phosphotyrosine-binding (PTB) domains of adaptor proteins including members of the insulin receptor substrate family (IRS) 10. This process leaded to the phosphorylation of important tyrosine residues on IRS proteins (IRS-1 and IRS-2), some of which were then recognised by a lipid kinase: PI3-kinase (PI3K). Insulin plays a key action in stimulating glucose uptake into cells by inducing translocation of the glucose transporter type 4(GLUT4) from cytosol to plasma membrane. PI3-kinase