Hyperglycemia

Prolonged hyperglycemia has a significant impact on the tissues of the body. A recent lead study by scientists from the United Kingdom revealed that hyperglycemia causes impairment in glucose metabolism, alters gene expression, and reduces β-cell mass.

 

Diabetes is one of the metabolic disorders which is characterized by alterations in insulin secretion from pancreatic β-cells. Usually, chronic elevation of blood glucose concentration (known as hyperglycemia) has deleterious effects on gene expression, metabolic pathways, autophagy of β-cells and glucotoxicity, thereby leading to glycogen accumulation. Several studies have examined the effect of hyperglycemia on β-cell structure and function both in vivo and in-vitro while some studied the duration and reversibility of hyperglycemia, or the mechanisms involved. The research work on impairment of insulin secretion and decrease in β-cells by researchers from the United Kingdom was published in the Nature Communications journal in 2016.




For investigating the progressive changes of β-cell dysfunction caused by hyperglycemia and its reversal, Ashcroft and his co-researchers, University of Oxford, United Kingdom carried out in-vivo studies on an inducible mouse model of neonatal diabetes (bV59M). Interestingly, activation of a mutation in the ATP-sensitive potassium (KATP) channel in the mouse model showed that KATP channels couple blood glucose levels to insulin secretion due to alterations in β-cell metabolism. Glycogen (the storage form of glucose) accumulation that led to increased β-cell apoptosis was observed to be mostly due to long-term diabetes. Analysis of mice expressing an activating mutation in glucokinase (GCK) has revealed that increased glucose metabolism drives changes in gene expression and glycogen storage.

In conclusion, hyperglycemia not only induces metabolic dysfunction in relation to gene expression, oxidative metabolism, ATP production and glycogen function in β cells, but also leads to loss of β-cells via apoptosis. In addition, diabetes present for short duration restores glycogen stores and β-cell metabolism. Generally, diabetes-inducing changes at gene expression level usually were not reversed but β-cells were more susceptible to a subsequent metabolic insult. It was also more difficult to reverse diabetes of longer duration. Further, following good glycemic control not only has a significant impact on the etiology and treatment of neonatal diabetes but also on other forms of diabetes.

 

Written By: Manche Santoshi, PhD




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