Mechanism of action of metformin is
**Core Concept**
Metformin is an oral antidiabetic drug used in the treatment of type 2 diabetes mellitus. Its mechanism of action involves the inhibition of hepatic gluconeogenesis, which is the process by which the liver produces glucose from non-carbohydrate sources.
**Why the Correct Answer is Right**
Metformin acts by inhibiting the mitochondrial respiratory chain complex I, which leads to a decrease in the ATP production and an increase in the AMP:ATP ratio within the hepatocytes. This increase in AMP:ATP ratio activates AMP-activated protein kinase (AMPK), which in turn inhibits the activity of key enzymes involved in gluconeogenesis, such as phosphoenolpyruvate carboxykinase (PEPCK) and fructose-1,6-bisphosphatase. As a result, the production of glucose by the liver is reduced.
**Why Each Wrong Option is Incorrect**
**Option A:** This option is incorrect because metformin does not primarily act by increasing insulin secretion or sensitivity.
**Option B:** This option is incorrect because metformin does not primarily act by blocking the reabsorption of glucose in the kidneys.
**Option C:** This option is incorrect because metformin does not primarily act by inhibiting the breakdown of glycogen in the liver.
**Clinical Pearl / High-Yield Fact**
It is worth noting that the use of metformin is contraindicated in patients with renal impairment or heart failure, as it can increase the risk of lactic acidosis.
**Correct Answer: C. Inhibition of hepatic gluconeogenesis via AMPK activation.**