1QQ# 4 for 10:30 1.Which cell type(s) have Glut-4 transporters? a) liver b) skeletal muscle c) adipose d) neurons 2.True or False: Excess amino acids are stored as glycogen in hepatocytes. 3.Which cell type(s) have insulin receptors? a) liver b) skeletal muscle c) adipose d) neurons

1QQ# 4 for 11:30 1.Which cell type(s) lack Glut-4 transporters? a) liver b) skeletal muscle c) adipose d) neurons 2.True or False: Excess amino acids are stored as triglycerides in adipocytes. 3.Which cell type(s) have insulin receptors? a) liver b) skeletal muscle c) adipose d) neurons

Fig Absorptive Phase Lipoprotein Lipase Once inside, glucose is converted to something else, thereby maintaining a concentration gradient for facilitated diffusion of glucose into cells. =“sinks” Entry requires Glut-4 transporters

Stimulatory actions of insulin in green Inhibitory actions of insulin in dashed red

? The Integrator integrates multiple inputs Glucose uptake, Storage, Lipogenesis WHY? FF Thinking about food, aroma, Factors that influence Insulin Secretion and other Incretins

Fig Post-absorptive phase Glucose Sparing Special case: Muscle wasting of starvation Note: Nervous tissue can use glucose and ketones Special term: Glycogenolysis & Gluconeogenesis Kidneys can convert amino acids to glucose!

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

Another hormone that regulates plasma glucose concentration Glucagon prevails during post- absorptive phase Transition from absorptive to post- absorptive phase?

Glucose-counterregulatory controls (oppose effects of insulin) Glucagon (target = hepatocytes) Epinephrine (liver, adipocytes, skeletal muscle) Cortisol (permissive effect for liver, adipocytes, skeletal muscle ) Growth hormone (permissive effect for liver, adipocytes, skeletal muscle )

Fig Post-absorptive phase Glucose Sparing Special case: Muscle wasting of starvation Note: Nervous tissue can use glucose and ketones Special term: Glycogenolysis & Gluconeogenesis Kidneys can convert amino acids to glucose! Insulin Receptor Adrenergic Receptor Cortisol Receptor Glucagon Receptor

Fig Don’t fret about receptors, afferent pathway, and integrator for this feedback loop. Adrenergic receptor

Who Cares?

A Case Study of Glucose Homeostasis A 35 year old male presented with the following complaints: frequent severe headaches upon awakening at 4:30 am, blurred vision, and fatigue due to excessive stress at work. The patient complained of routine 16 hr workdays followed by a midnight snack of breakfast cereal. An OGTT was ordered and provided the following results: During the second hour of the OGTT, the patient exhibited anxiety, paleness, hunger, tremulousness, and cold sweat. No additional tests were ordered. The patient was instructed to replace the midnight snack of cereal with a protein-rich snack.

Oral Glucose Tolerance Test Overnight fast, no beverages other than water Fasting blood sample Ingest 75 grams glucose Blood samples every 0.5 hours for 3-5 hours Plot plasma glucose concentration over time Compare curves Sugar content of Red Bull?

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Stress, Emergency (fight or flight) Effect on Beta cells Effect on Alpha Cells

The Answer to the Problem? Rationale for substituting protein for carbohydrate midnight snack?