1QQ # 4 Name on top edge, back side of paper Answer on blank side of paper. Answer one of the following: 1. Why is light colored, loose fitting clothing that covers the entire body except face and hands optimal for desert dwellers? 2. Explain how it is possible to kill a comatose person by covering them with excessive blankets.

Plasma Glucose Homeostasis Widmaier et al., p Glucose metabolism Hormonal Control Disruptions of glucose homeostasis A Case Study

Homeostasis of Plasma Glucose Concentration Normal physiological range: mg/dl What is the set point? Why is too much plasma glucose harmful? Plasma glucose concentration = glucose entering the plasma – glucose leaving the plasma What are the mechanisms that regulate plasma glucose concentration? What are the components of the negative feedback loop: –Glucose receptors? –Afferent pathway? –Integrator? –Efferent pathway(s)? –Effector organ(s)? Phases: *absorptive, *post-absorptive, and fasting

Graph your daily caloric intake over a 48 hour period 6am 6pm Noon MN Calories consumed 6am Noon Plasma Glucose ? ? Overlay absorptive and post-absorptive phases on the graph

Fig =sink Absorptive Phase Hepatic Portal System Lipoprotein Lipase Once inside, glucose is converted to something else, thereby maintaining a concentration gradient for facilitated diffusion of glucose into cells.

Islets of Langerhans Alpha cells secrete glucagon Beta cells secrete insulin Delta cells secrete somatostatin Hepatic portal system Route of blood Liver

Fig Post-absorptive phase Glucose Sparing Special case: Muscle wasting of starvation Note: Nervous tissue can use glucose and ketones

Major Points Absorptive phase lasts ~ 4 hours During absorptive phase, energy needs provided by recently digested food During absorptive phase, excess is converted to stored fuel During post-absorptive phase, energy need met by release of stored fuels Fasting defined as greater than 12 hours after previous meal (some say 24 hrs) Fasting for several days has little effect on plasma glucose levels

The Issues How do cells “know” which fuel to “burn?” How do cells “know” when to synthesize glycogen or lipids and when to break down glycogen or lipid? What is responsible for the transitions from the absorptive and post-absorptive states? How does glucose get into “sink” cells?

Activates some enzymes, inactivates others GLUT-4 Peptide hormone Exercise (via an undescribed mechanism) increases the number of glucose transporters in muscle cell membrane + Diabetes mellitus: T1DM =beta cells fail to produce adequate insulin (5%) T2DM = target cells “resistant” (less responsive) to insulin ↑ plasma glucose →↑insulin secretion→↑glucose uptake into cells →↓ plasma glucose

Questions based on this lecture What is the difference between the post-absorptive phase and fasting? What is the normal range for plasma glucose concentration? (include the units.) During the absorptive phase, what is the fate of –Excess amino acids –Glucose that enters the liver –Glucose that enters adipose tissue –Glucose that enters muscle tissue What is the role, source, and destination of VLDLs during the absorptive phase? What is the location and role of lipoprotein lipase? What is the main cellular fuel used by most cells during the absorptive phase? What marks the end of the absorptive phase? What tissues are the sinks of glucose during the absorptive phase? Which of these constitutes the largest “sink?” How long does the absorptive phase typically last? During the absorptive phase, is there net anabolism or net catabolism of triglycerides?

Questions based on this lecture How is the gradient maintained that favors the entry of glucose into cells? What is the name of the molecule that is polymer of glucose and which cell types can have this polymer? What is a portal system? What is the function of the hepatic portal system? How do cells of the liver alter the blood that arrives there from the digestive tract? The pancreas is actually two glands in one. What are the two glands and what is the function of each? What are the names and secretions of the two most important cell types of the Islets of Langerhans? Speculate as to why pancreatic cancer has a very high mortality rate? During the post absorptive phase, what is the fate of amino acids released from muscle tissue? During the post absorptive phase, what other molecules are release from muscle cells and what is the fate of these molecules? During the post absorptive phase, what is the source of glycerol entering the plasma? Where does that glycerol go and what is its fate?

Questions based on this lecture What is the first source of glucose during the early portion of the post absorptive phase? What is gluconeogenesis? What is glycogenolysis? What is/are the predominate fuel molecules used by most cells during the post absorptive phase and during fasting? What are the only two molecules that can be used as fuel by the nervous system? What is meant by the term “glucose sparing?” By what means is plasma glucose maintained in or near the normal range even with prolonged fasting of 1-2 weeks? Which two hormones would be expected in large amounts in the blood of a fasting person? (Didn’t cover this yet, but figure it out.) How might the composition of a meal (protein, carbohydrate, fats) be related to the duration of the absorptive phase? Since insulin is a peptide hormone, where must the receptors for insulin be situated on “sink” cells? Do neurons have insulin receptors? If not, how do neurons take up glucose? What is sequence of cellular events that is initiated by the binding of insulin to insulin receptors?

Questions based on this lecture By what means can the uptake of glucose from the plasma be finely adjusted in proportion to the amount of glucose in the meal? Are the levels of insulin high or low during a fast? During prolonged exercise during a fast, insulin levels would be very low, yet muscle cells can still take up glucose. How can they do so? Why is exercise recommended for persons who tend to have elevated plasma glucose? Explain how an overdose of insulin could result in loss of consciousness and even death? On the graph that shows the 48 hour intake of food and the fluctuations of plasma glucose, add a plot that shows the expected levels of insulin in the plasma.