Chapter 19

A variety of metabolic parameters affect homeostatic blood glucose levels. For each of the altered metabolic conditions listed below, predict if it would result in higher or lower blood glucose levels compared to that of the normal metabolic condition. a. Amino acids are not efficiently converted to keto acids during starvation. b. Glycogen debranching enzyme does not function during intense exercise. c. The glucagon receptor is always active, even in the absence of glucagon. d. The enzyme pyruvate carboxylase is expressed at abnormally high levels. e. Pancreatic $\alpha$ cells do not secrete functional glucagon.

In addition to stimulating uptake of excess blood glucose into adipose, insulin stimulates fatty acid synthesis and storage of triacylglycerols in adipose. On the basis of these insulin effects, why is it a bad idea to eat six sugar donuts before a 60 -mile bike race to get "energy" for the 3-hour

Fasting studies performed in an animal model showed that rates of muscle protein hydrolysis change dramatically in the first 7 days. In the first 24 hours, the rates of protein hydrolysis were low, but then increased substantially for the next $3-4$ days. By day $5,$ the rates of protein hydrolysis decreased to much lower levels for the duration of the fast. Given that there are no known regulatory mechanisms controlling muscle protein hydrolysis, how can you explain this pattern?

On the basis of the premise of the thrifty gene hypothesis, predict if the following hypothetical gene variants would be candidate thrifty genes. Explain your answer. a. Acetyl-CoA carboxylase that is insensitive to feedback inhibition by palmitoyl-CoA b. Insulin receptor that has an increased affinity for insulin c. High basal levels of uncoupling protein in liver cells d. A hyperactive lipoprotein lipase on the plasma membrane in adipose cells e. A hyperactive hormone-sensitive lipase on lipid droplets in adipose cells

One of the effects of leptin in nonadipose tissue is to upregulate the synthesis of uncoupler protein. How might this effect help prevent obesity?

Leptin is an adipocyte hormone that sends signals to the brain to "eat less" and "metabolize more." What is the explanation for why leptin injections cause weight loss in the strain of OB mutant mice, but leptin injections have no effect in the majority of obese people? Is this observation analogous to type 1 or type 2 diabetes? Explain.

On the basis of the function of ghrelin and ${\mathrm{PYY}}_{3-36}$, explain why it is good advice to eat slowly if you are trying to lose weight.

Treatment of type 2 diabetes to lower blood glucose includes the use of sulfonylureas, which stimulate insulin secretion, and metformin, which inhibits gluconeogenesis. Explain the biochemical rationale behind the use of each drug.

What is the biochemical explanation for the high level of ketone bodies in untreated diabetics?

What explains the often-encountered side effect of "acetone breath" on dieters following a very strict low-carbohydrate diet such as the Atkins Diet?