Thursday, November 15, 2012



Genetic factors contribute to development of T-2 diabetes, thus T-2 diabetes is termed as geneticist’s nightmare. T-2 diabetes is 10 times more likely to occur in obese person with a diabetic parent than an equally obese person without a diabetic family history. Diabetes is multiple gene disorder and the pattern of inheritance is complex. The known genes involved in T-2 diabetes can be separated into those involved in insulin secretion, those participating in insulin action and those regulating body weight.

Fig. Causes of Type 2 Diabetes
In MODY characterized by nonketotic diabetes, there is asymptomatic hyperglycemia to acute presentation. There are different types of MODY resulting from mutations in genes that encode glucokinase or several other transcription factors.

Numerous mutations in insulin receptor genes have been identified resulting in extreme insulin resistance, e.g. GLUT4.

A gene that is expressed only in adipose tissue (ob) has been identified and its product leptin has been proposed to be vital signaling factor regulating body weight homeostasis and energy balance. Leptin is synthesized in adipose tissue and binds to specific receptors in hypothalamus, regulating appetite and energy intake. Plasma leptin increases during hyperglycemic conditions and both food intake and insulin increases leptin mRNA. Thus insulin is important factor for regulating food intake and ob expression providing possible link between obesity and type 2 diabetes.


Amylin is believed to regulate glucose metabolism by delaying gastric emptying and suppressing glucagon production. It is called islet amyloid polypeptide, IAPP is a peptide co-secreted with insulin by β-cell in all subjects with intact insulin secretion (but not those with type 1 diabetes) in response to food ingestion. It is suggested to have role in regulation of insulin secretion within pancreatic islet cells. Amylin fibrils are found deposited in islet cells during excess insulin secretion (as in insulinoma) which may causes islet damage in type 2 diabetes.
β-cell dysfunction:
There is hyperinsulinaemia during fasting. There is defect in pulsatility of insulin secretion and early insulin response to glucose. With time hyperinsulinaemic individual becomes insulin deficient and needs exogenous insulin treatment, because β-cell become exhausted or damaged due to their hyperactivity due to hyperglycemic drive. Due to this dysfunction the early release of insulin or the first phase of insulin release is defective.
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