The pancreas and blood glucose

Endocrine glands are ductless: their hormones enter the interstitial fluid and then the blood. Exocrine glands, such as sweat glands, release their products through ducts.

• Endocrine glands release their products into ducts that open onto a surface:
• Correct: Endocrine glands release hormones into the blood, with no ducts:
• Endocrine glands are found only in the brain:

A carrier protein that moves a molecule down its concentration gradient without spending ATP carries out facilitated diffusion.

• Correct: Facilitated diffusion:
• Primary active transport:
• Osmosis:

Water-soluble hormones bind receptor proteins in the plasma membrane. The receptor protein then starts a chain of signals inside the cell, such as cyclic AMP and protein kinases, which change existing proteins within seconds to minutes.

• It binds a receptor protein inside the nucleus and switches on genes directly:
• Correct: It binds a receptor protein on the cell surface, which sets off a second-messenger or enzyme cascade inside:
• It dissolves in the membrane and changes its shape:

Insulin release depends on ATP closing these channels. With them held open, potassium keeps leaking out, the membrane cannot depolarize, voltage-gated calcium channels stay closed, and without calcium entry the insulin vesicles are not released.

• Correct: The membrane stays polarized and insulin release falls: Correct. With the channels held open, potassium keeps leaking out, the membrane cannot depolarize, voltage-gated calcium channels stay closed, and without calcium entry the insulin vesicles are not released.
• Potassium flows into the cell and insulin release rises: Open potassium channels let potassium flow out, down its gradient, not in. Outward flow keeps the inside negative, which works against depolarization.
• Glucose entry stops and insulin release falls: The drug acts on the potassium channel, not on glucose entry. Glucose still enters and raises ATP; the step after ATP is blocked.
• The membrane depolarizes more easily and insulin release rises: Depolarization needs the potassium channels to close. Holding them open does the opposite.

Insulin rises within minutes of the meal and peaks with glucose. It moves GLUT4 into muscle and fat membranes and makes the liver store glucose as glycogen, so glucose leaves the blood. As glucose falls, insulin falls too: negative feedback.

• Glucagon rising after the meal: Glucagon falls after a carbohydrate meal, and it would raise blood glucose, not lower it.
• Correct: Insulin driving glucose into cells: Correct. The insulin curve rises and falls with the glucose curve.
• The kidneys excreting the extra glucose in urine: Glucose appears in the urine only above about 180 mg/dL. This person peaks near 135, so the kidneys return all of it.
• The brain burning the meal's glucose: The brain uses glucose at a steady rate of about 5 grams an hour. That alone cannot clear a meal's 50 grams or more in two hours.

Losing insulin raises glucose; losing the beta cells' brake raises glucagon too. Glucose spills into the urine and drags water with it, shrinking blood volume and driving thirst. Fat breakdown runs unchecked, the liver turns the fatty acids into acids that build up in the blood, and breathing deepens to blow off carbon dioxide. Untreated, this becomes a life-threatening emergency.

• Blood glucose: up. With no insulin, muscle and fat take up little glucose and the liver keeps releasing it.
• Plasma glucagon: up. Insulin from neighboring beta cells normally damps the alpha cells. With the beta cells gone, that brake is lost.
• Glucose in the urine: up. Blood glucose is above the roughly 180 mg/dL the kidney's carriers can fully reabsorb, so the excess stays in the urine.
• Urine volume: up. Glucose left in the kidney's fluid holds water there by osmosis: polyuria.
• Blood volume: down. Water lost in the extra urine comes from the plasma.
• Body weight: down. Calories leave as urine glucose, and with no insulin, fat and muscle are broken down.
• Blood pH: down. Unchecked fat breakdown and high glucagon make the liver turn fatty acids into acids faster than tissues can burn them.
• Depth and rate of breathing: up. Acid in the blood drives faster, deeper breathing, which blows off carbon dioxide and partly offsets the acid.

The brain runs almost entirely on glucose from the blood, minute by minute. Muscle can burn fatty acids and its own glycogen, so it keeps working when blood glucose falls.

• Neurons need insulin to take up glucose, and insulin is low: Neurons take up glucose through carriers that are always in their membranes, with no need for insulin.
• Low glucose triggers a sympathetic discharge that shuts down the brain: The sympathetic response causes shakiness, sweating and a fast heart. It does not shut down the brain; the lack of glucose does.
• Muscle makes glucose by gluconeogenesis and shares it with the brain: Gluconeogenesis happens in the liver and, in a long fast, the kidneys. Muscle cannot release glucose into the blood.
• Correct: Neurons have almost no glycogen and burn almost no fatty acids: Correct. The brain has no fuel reserve and no fallback fuel for sudden lows, so it depends on glucose from the blood minute by minute.

Above about 180 mg/dL, the kidney's carriers cannot take back all the filtered glucose. The glucose left behind holds water by osmosis, so more water leaves as urine. The thirst comes after, from the water lost.

• Correct: Glucose in the kidney's fluid holds water there by osmosis: Correct. The glucose drags water with it: polyuria.
• High blood glucose blocks the release of ADH from the posterior pituitary: High glucose raises plasma concentration, which increases ADH release, not decreases it.
• Insulin normally tells the kidneys to keep water: Insulin does not control water handling by the kidneys. Its absence acts through the high glucose.
• Drinking more, which the kidneys then excrete: That gets the order backwards. The water loss comes first and causes the thirst.

High glucose together with high insulin means her tissues respond too little to insulin: insulin resistance. Her beta cells are releasing extra insulin but can no longer keep glucose normal. That is type 2 diabetes. A fasting glucose of 126 or above, confirmed on a second test, meets the diagnostic cutoff.

• Type 1 diabetes: In type 1 diabetes the beta cells are destroyed and insulin is very low or absent, not high.
• Hypoglycemia from excess insulin: Her glucose is high, not low. The high insulin is failing to lower it.
• Correct: Type 2 diabetes with insulin resistance: Correct. High glucose despite high insulin is the signature of insulin resistance.
• Normal glucose control: A fasting glucose of 138 mg/dL is well above the normal range of 70 to 99.

Skeletal muscle has almost no glucagon receptor proteins and lacks the enzyme that lets glucose leave the cell. Between meals, blood glucose comes from the liver.

• Blood glucose falls toward the low end of its range: This step is right. Tissues keep using glucose between meals, so it drifts down.
• Alpha cells release more glucagon, and beta cells release less insulin: This step is right. Low glucose stimulates alpha cells and quiets beta cells.
• Glucagon binds receptor proteins on liver cells, and cyclic AMP rises: This step is right. Glucagon acts through a G protein–coupled receptor protein and cyclic AMP.
• The liver switches on glycogenolysis and gluconeogenesis: This step is right. The liver releases stored glucose and makes new glucose.
• Correct: Glucagon makes skeletal muscle release glucose from its glycogen into the blood: This is the error. Muscle glycogen stays in the muscle; only the liver releases glucose into the blood.

Gluconeogenesis: gluc/o = glucose, neo- = new, -genesis = making. The liver does most of it.

• Glycolysis: Glycolysis is the breakdown of glucose in cellular respiration, the opposite direction.
• Correct: Gluconeogenesis: Correct. New glucose from molecules that are not carbohydrates.
• Glycogenesis: Glycogenesis is building glycogen, the first term in the list.
• Cellular respiration: Cellular respiration breaks fuel down to make ATP. It uses glucose rather than making it.