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Hepatic Glucose: Role of the Liver in diabetes

Hepatic glucose output

For a normal individual, low blood sugar is uncomfortable. But it is not dangerous and termed as Hunger. In a diabetic individual, the same feeling can be threatening. Our body maintains a blood-sugar level within the desired range throughout the day.

Insulin secretion, Insulin resistance, and hepatic glucose production are the 3 basic core defects of diabetes. For a diabetic individual, understanding these concepts is very important to monitor glucose levels. Hepatic glucose production is the formation of glucose in liver cells. It is regulated by hormones Insulin and Glucagon. In today’s write up, we will overview the role of the Liver in Glucose Homeostasis.

Glucose Homeostasis

Ingested food raises blood glucose levels rapidly. These excess blood glucose molecules enter in Beta cells of the pancreas. Thus, Beta cells secrete insulin to bring down excess blood glucose to normal. Elevation of glucose levels in the blood primarily stimuli insulin secretion. The insulin suppresses the raised blood glucose levels and Glucagon secretion.

Alpha cells of pancreas secrets Glucagon. It has ‘Glucose agonist’ properties. In the Liver, glucagon acts as a counter-hormone for insulin. An excess of glucagon definitely contributes to a rise in blood glucose. The role of glucagon is to prevent the lowering of blood glucose too low. Glucagon stimulates the conversion of glycogen to glucose. This glucose then released into the blood again.

The Liver plays a key role in regulating both glucose and lipid metabolism. Maintaining a striking balance between glucose uptake and endogenous glucose production is very much essential for glucose homeostasis.

Blood glucose and Liver

Diabetics might often felt the mid-afternoon or mid-night crash in blood glucose levels. This means the glucose levels are too low in the bloodstream and fallen below normal. When there is low glucose, the brain signals the release of glucagon hormone. It stimulates the release of stored glucose from the Liver. And thus endogenous glucose gets secreted into the blood.

The liver stores the excess amount of glucose in the form of glycogen. It provides the body with a readily available source of energy if blood glucose levels decrease. Storage of glucose is due to high levels of insulin and suppressed levels of glucagon. Glycogen can be used for a later time when your body needs it.

Controlling the amount of glucose circulating in the blood one of the liver’s main roles in the body. When the food is ingested in our body;

 In normal Individual In Diabetics
1Increased Glucose LevelsIncreased Glucose levels
2Beta cells stimuliImpaired Beta cells stimuli
3Insulin secretionLess/No insulin secretion
4Glucose Uptake By cells (No insulin Resistance)Poor glucose Uptake by cells (Insulin Resistance)
5Glucose levels suppressedGlucose levels incite
6Glucagon SuppressedGlucagon incites
7Excess Glucose stored in LiverExcess glucose release from Liver
8Normal Blood glucose levelsThe rise in blood glucose levels

The Liver acts as a reservoir and manufacturer of glucose. It helps to maintain blood glucose levels within the normal specified range when needed. Blood glucose levels drop when you’re not eating, such as during sleep or between meals. This low blood sugar signals the liver to produce glucose and release it back into the bloodstream.

Dysregulated Hepatic Glucose production

Hepatic glucose production is a normal daily metabolic pathway useful for allowing intermittent feeding without disrupting the glucose supply to the body. It provides a rapid supply of glucose to the body to prevent the development of hypoglycemia, such as with an overnight fast.

Unfortunately, excessive hepatic glucose production has been observed in a number of settings of uncontrolled type 2 diabetes, thus contributing to worsening of the hyperglycemia.

Factors involved in this dysregulation of hepatic glucose production include;

  1. Delayed and diminished insulin secretion (both the first phase and second phase) inadequate for glucose levels.
  2. Excessive glucagon production which is not suppressed postprandially and has higher levels in the basal state.
  3. Impairment of glucose uptake/disposal in the splanchnic circulation allowing more glucose into the general circulation.
  4. Impaired suppression of glucose production in the liver by circulating glucose and insulin.

Gluconeogenesis and Glycolysis

When you are fasting or on a low-carbohydrate diet, levels of glycogen get low. In this case, the liver uses alternative sources to produce and release more glucose into the bloodstream.

When glycogen levels drop, the Liver uses fats to create ketones. Ketones also act as a fuel for muscles and other body organs.

  • Gluconeogenesis is the generation of glucose from non-carbohydrate carbon substrates, proteins, and fat byproducts.  It occurs in the liver, kidney, and epithelial cells of the small intestine. 90% of the process occurs in the Liver.
  • Glycolysis is the breakdown of glucose by enzymes, releasing energy for cellular metabolism. It occurs in the cytosol of a cell.

Moreover, in diabetics, both of these processes further leads to the accumulation of glucose in the blood. Also, insulin resistance is the leading cause of rising glucose levels in Type 2 diabetes. It is essential to know how to reverse insulin resistance.