A 43-year-old man is hospitalized due to severe epigastric pain radiating to his back. He does not drink alcohol. Temperature is 37.9 C (100.2 F), blood pressure is 114/68 mm Hg, and pulse is 85/min. BMI is 34 kg/m². The patient appears restless. Physical examination shows significant epigastric tenderness. Laboratory results are as follows: Administration of intravenous fluids and analgesics is begun. In addition, insulin is administered to rapidly reduce the elevated lipid levels. This medication is likely to improve this patient's condition by stimulating which of the following enzymes?

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11ec160b_3bcf_1083_9249_af874d1441e3_MD0001_00 This patient has acute pancreatitis presenting with abdominal pain, epigastric tenderness, and an elevated serum amylase level. In addition, he has severe hypertriglyceridemia, which is the likely cause of his pancreatitis. Triglyceride-induced pancreatitis (TIP) is usually seen in patients with triglyceride levels >1,000 mg/dL. The risk is elevated in patients with diabetes mellitus, obesity, or excessive alcohol use. TIP is initiated by impaired blood flow in pancreatic capillaries due to excessive concentrations of chylomicrons and VLDL particles. The resulting tissue ischemia releases pancreatic lipases into the plasma, hydrolyzing triglycerides to yield very high local concentrations of inflammatory free fatty acids. Management of TIP requires rapid lowering of triglyceride levels, often with an insulin infusion. Insulin upregulates lipoprotein lipase, which hydrolyzes triglycerides in chylomicrons and VLDL; the liberated fatty acids are largely taken up and esterified in adipose tissue, and plasma triglyceride levels are lowered. In addition, insulin reduces the activity of hormone-sensitive lipase in adipose tissue (Choice B), suppressing the release of fatty acids. (Choice A) AMP-activated protein kinase (AAPK) suppresses sterol regulatory element-binding protein-1 and acetyl-CoA carboxylase, leading to decreased hepatic fatty acid synthesis and VLDL production. Metformin stimulates AAPK, leading to suppression of lipogenesis and lower circulating triglyceride levels. However, insulin does not increase AAPK activity. (Choice C) HMG-CoA reductase catalyzes the rate-limiting step in cholesterol production. Insulin increases the activity of HMG-CoA reductase, promoting increased cholesterol synthesis; increasing HMG-CoA reductase activity will not lower serum triglyceride levels. (Choice E) Pyruvate carboxylase catalyzes the conversion of pyruvate to oxaloacetate, which can be used to drive lipid synthesis (citrate-malate shuttle) or diverted to gluconeogenesis. Insulin downregulates (not upregulates) its activity in the liver, leading to reduced gluconeogenesis and hepatic fatty acid production. Educational objective: Triglyceride-induced pancreatitis is initiated by impaired blood flow in pancreatic capillaries due to excessive concentrations of chylomicrons and VLDL particles. Insulin upregulates lipoprotein lipase (an enzyme that hydrolyzes triglycerides in chylomicrons and VLDL) in adipose tissue capillaries; the liberated fatty acids are taken up by adipose cells, lowering serum triglyceride levels. __________ References: Hypertriglyceridemic pancreatitis treated with insulin therapy: a comparative review of 34 cases. (http://www.ncbi.nlm.nih.gov/pubmed/30648042)

A 43-Year-Old Man Is Hospitalized Due to Severe Epigastric Pain