how the biochemistry of regulation is affected by the acute effects of metformin

Based on the literature, fructose 1,6-bisphosphatase (FBPase) is a potential target for metformin. Demonstrate your understanding of glucose metabolism to show why this is the case when treating T2DM. Include in your answer how the biochemistry of regulation is affected by the acute effects of metformin. 

Answer:-

Metformin is a commonly used diabetic drug. This is derived from the compound galegine from the plant Galega officinalis. Metformin has an antidiabetic effect. It inhibits the hepatic gluconeogenesis and primarily inhibits the fructose 1,6-bisphosphatase enzyme (LaMoia & Shulman, 2021)

Gluconeogenesis is an intensive reaction primarily managed by the hepatic cells. The metformin molecule ensures to accumulates in the mitochondria than in the cytoplasm.  The complex I in the mitochondria are inhibited in the respiratory chain and suppresses the sysnthesis of the adenine triphosphate that is further involved in the activation of the process. There is remarkable drop in the concentration of the ATP molecules than the ADP in the cells. (Rena et al., 2017). The type 2 diabetes is primarily involved in the loss of control over the glucose levels due to increased insulin resistance. The metformin works in an indirect manner through the reduction in the glucose levels through restriction of hepatic metabolism and thereby managing the blood glucose. In the liver, the drug Metformin, inhibits the enzyme AMP kinase which is directly involved in the glycogen synthesis and thereby reducing the hepatic energy metabolism. Another method of glucose disposal is noted in the case of Metformin, i.e., the peripheral skeletal muscle metabolism. The fructos-6-phosphatase is one of the key regulators of the glusose breakdown. It is also involved in the glucosneogenesis in the liver. The FBP is inhibited by the presence of AMP thus the restriction of the ADP production in the mitochondria by blocking the complex I is aimed at the accumulation of the AMP. This has been proved by the studies involving the frustose2,6-phosphatase and knock out mice. Metformin is predominantly known to act against the hyperglycemic condition and has been observed in high fat diets. The striking feature of the diabetes type 2 is hepatic steatosis as a result of chronic exposure to glucose concentrations. The half life of metformin is typical between 1.5 to 4.5 hours after administration. The presence of AMP is a direct indicator of the metabolic stress and can cause hypoxia.

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