A 24-year-old man diagnosed with diabetes mellitus 2 years ago is brought to the emergency department after a temporary loss of consciousness. He was getting ready to eat and administered a preprandial insulin injection, but he was distracted by a phone call from work and ended up skipping the meal. His girlfriend found him passed out in his bedroom and administered glucagon immediately. The patient recovered consciousness within 15 minutes. Metabolic changes in which of the following organs are most likely responsible for this patient's recovery?

Question

A 24-year-old man diagnosed with diabetes mellitus 2 years ago is brought to the emergency department after a temporary loss of consciousness.  He was getting ready to eat and administered a preprandial insulin injection, but he was distracted by a phone call from work and ended up skipping the meal.  His girlfriend found him passed out in his bedroom and administered glucagon immediately.  The patient recovered consciousness within 15 minutes.  Metabolic changes in which of the following organs are most likely responsible for this patient's recovery?

Quizplus · Accepted Answer

Glucagon increases serum glucose by increasing hepatic glucose production via glycogenolysis (breakdown of glycogen) and gluconeogenesis (production of glucose from noncarbohydrate sources). Glucagon-induced glycogenolysis is the predominant initial means of rapidly increasing blood glucose levels during hypoglycemia. Glucagon functions by stimulating G protein-coupled receptors on hepatocytes, increasing intracellular cAMP concentration and activating protein kinase A. This leads to activation of the key glycogenolytic enzyme, glycogen phosphorylase. It also stimulates gluconeogenesis by activating rate-limiting gluconeogenetic enzymes (eg, pyruvate carboxylase, phosphoenolpyruvate carboxykinase) and decreasing intracellular fructose-2,6-bisphosphate levels (inhibiting glycolysis). (Choices A, B, and F) Epinephrine from the adrenals increases glucose by multiple mechanisms, including increased glycogenolysis and gluconeogenesis in the liver and decreased glucose uptake by skeletal muscle. Epinephrine also causes increased alanine release from skeletal muscle, which serves as a source of gluconeogenesis in the liver. In adipose tissue, epinephrine increases the breakdown of triglycerides, thereby increasing circulating free fatty acids and glycerol that can be utilized as gluconeogenetic substrates. (Choice C) During the first 12 hours of fasting, hepatic glycogenolysis is the source for most of the body's glucose. When hypoglycemia is sustained, gluconeogenesis in the renal cortex becomes an important glucose source. Epinephrine is more effective than glucagon in stimulating renal gluconeogenesis. (Choice E) Glucagon and insulin are pancreatic hormones that act as key blood glucose regulators. Insulin decreases blood glucose levels and suppresses glucagon secretion. Although it sounds counterintuitive, glucagon stimulates insulin secretion by acting on the pancreatic beta cells (allowing glucose to be taken up by insulin-sensitive tissues). (Choice G) The treatment of choice in hypoglycemic patients without an altered sensorium is to administer glucose orally as glucose is a monosaccharide that gets absorbed rapidly from the gastrointestinal tract. Educational objective: Glucagon increases serum glucose by increasing hepatic glycogenolysis and gluconeogenesis. Glucagon also stimulates insulin secretion from the pancreas. Unlike epinephrine, glucagon has an insignificant effect on glucose homeostasis in the skeletal muscle, adipose tissue, and renal cortex. __________ References: Physiologic action of glucagon on liver glucose metabolism. (http://www.ncbi.nlm.nih.gov/pubmed/21824265)

A 24-Year-Old Man Diagnosed with Diabetes Mellitus 2 Years Ago