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Role of glucose in regulating liver functions

Date: 15 March 2020 Tags: Miscellaneous

Issue

A study by researchers from Tata Institute of Fundamental Research, Mumbai (TIFR) shows that glucose controls the function of SIRT1 directly, which in turn is responsible for major functions of liver.

 

Background

 Studies have shown that metabolic diseases are associated with wrong feeding regimen. Every organism has evolved so as to feed and then alternately fast, so it becomes important to understand this cycle. This cycle, known as the feed-fast cycle is a basic pattern and the metabolism related to this is largely taken care of by the liver.

 

Details

  • A shortage or absence of this control can lead to a diabetic-like state, while excess feeding and sustained low levels of SIRT1 can lead to obesity and enhanced ageing.

  • The enzyme, SIRT1, is known to be associated with regulation of metabolic activities and also ageing and hence has become a target of therapeutics.

  • The group has discovered that glucose controls the functions of a protein SIRT1 which in turn maintains everyday feed-fast cycles and is also associated with longevity.

  • Despite decades of work on the beneficial roles of SIRT1, metabolic factors that decrease its functions both during normal feed-fast cycles and in nutrient excess states (like obesity) was unknown.

  • While there is active research to identify drugs that can activate SIRT1 which would be beneficial in countering ageing and metabolic diseases, the cost of uncontrolled overactivation of SIRT1 has not been investigated especially since it decreases in a healthy individual in a fed state.

  • Glucose puts a check on the activity of SIRT1 in the fed state. In the absence of this check, SIRT1 activity increases and results in hyperglycaemia in a fasted state, mimicking diabetic state.

  • Constant feeding or high calorie intake that leads to sustained reduction in the levels of SIRT1 (by glucose) is associated with ageing and obesity.

  • This study paves the way to regulating this modification, which might be beneficial in tackling lifestyle disorders and ageing related diseases.

  • The group next seeks to investigate if glucose-dependent control can dictate gene expression during feed-fast cycles.