Ishita TA: Desai
Handout #8 TA Version
GLP-1 and GIP are incretins that STIMULATE/INHIBIT the secretion of insulin.
What are the numerous effects of insulin?
Inc glucose uptake by adipose and skeletal muscle (inc glut 4)
Liver: inc hexokinase activity (glu + ATP --> G6P + ADP)
Stimulation of glycogen synthase --> inc glycogen
Inhibition of glycogen phosphorylase (glyco breakdown)
Inc tryglycerides (lipogenesis)
Dec hormone sensitive lipase
Inc AA uptake and protein syn
dec beta ox pathway --> ketones (acetoacetic acid and betahydroxybutyric acid;
acetone)
Dec gluconeogenesis
What stimulates and inhibits the release of glucagon?
Stimulants: decreased glucose, increased sympathetic
Inhibitors: increased glucose, insulin, somatostatin, incretins
What are the not-so-numerous effects of glucagon?
Increase glycogen phosphorylase --> glycogen breakdown
Inc G6P phosphatase --> G6P + H2O --> glucose + Pi
Inc gluconeogenesis (from aas and ffa)
Inc hormone sensitive lipase
Inc proteolysis
DIABETES
What are the mechanisms for polydipsia and polyuria?
- Increased blood glucose Increased osmolarity ADH, thirst (polydipsia)
- Glucose above 300mg/dL (proximal tubule has SGLTs to reabsorp glucose)
glucose lost in urine increases urine osmolarity increases H2O lost in urine
polyuria/glusouria dehydration increased osmolarity of blood
polydipsia
Polyphagia is the third P of diabetes. This is because glucose is not metabolized signals
hunger.
What allows for HbA1c levels to be a good measure of BGL over the course of the past few
months?
Hb reacts/binds with glucose (high concen) --> measure HbA1C levels
Glycated Hb circulating for abt 130days - - - normal is less than 6%
Diabetic ketoacidosis is a serious problem for type I diabetics. The mechanism behind the
problem is:
Increased BGL increased blood osmolarity glucos/polyuria decreased BP inc
HR circu shock
- Glucose is not available as a form of energy (for brain!) increased fatty acid betaoxidation -> increase ketoacids (acetoacetic and OH-butyric acids) dec blood pH
TA: Ishita Desai
metabolic acidosis (ketoacidosis) CNS depression (lose consciousness/coma),
hyperventilate (until remove CO2), acetone breath
o Tx with insulin and hydration (w/electrolytes)
HYPOGLYCEMIA
- BGL less than 60-70mg/dL
- What are the symptoms?
o Sleepiness, irritation, increased sympathetic stimulation (pale, tachycardia,
sweating, vasoconstriction, increased BP)
- BGL b/w 30-40
o More extreme versions of pervious symptoms + confusion/loss consciousness
- <30
o Seizures, death
What ONE thing causes apple shaped individuals to be susceptible to Type II Diabetes?
Increased size of abdominal increased adipocytes resistin secretion + decreased
adiponectin secretion
What are symptoms of metabolic syndrome?
Obesity, high BP, increased TGLs
What will a glucose tolerance test of someone with metabolic syndrome look like as opposed to
a normal person?
Higher than normal fasting BGL and spike is higher as well as a very delayed return to
normal
Evan is overweight, and occasionally feels excessively hungry and thirsty. Theres really only
one possibility for his disorder from what weve learned in the past hourso lets skip that and
ask about treatments. What are the three possible ways in which to treat Evans disorder?
- Increase insulin secretion (sulfonyl ureas, incretins, inhibitors of dipeptidase
increase incretins)
- Decrease insulin resistance
o (target PPAR (peroxisome proliferation activated Rs) activated by
polyunsat fatty acids
PPAR gamma agonists
Avandia side-effects!!!
o Increase adiponectin (inc metabolism and insulin sensitivity)
o Dec secretion of resistin
- Dec gluconeogen
o Biguanides (metformin)
o Decrease glucose load of body
An obese patient was found to have increased plasma triglycerides and hypertension; a glucose
tolerance test showed fasting glucose = 100 mg/dL but after 2 hours the glucose was
190mg/dL. Your diagnosis?
A. TYPE II DIABETES
B. TYPE I DEABETES
C. METABOLIC SYNDROME
D. Any of the above
E. None of the above
TA: Ishita Desai
Which of the following will allow you to tell whether a person with severe polyuria has diabetes
mellitus or insipidus?
A. Dehydration
B. Hypotension
C. Very low osmolarity of the urine
D. Thirst
E. All of the above
Which of the following is NOT a metabolic effect of glucagon?
A. Inc gluconeogenesis
B. Inc lipolysis
C. Inc glycogen phosphorylase activity in liver and muscle
D. Inc hormone sensitive lipase
E. Inc glucose-6-phosphatase in muscle
Which of the following is false about insulin effects in the liver?
A. GLUT 4 (remember these are in skeletal and adipocytes; GLUT 2 is LIVER; GLUT3
neurons; GLUT1 in RBCs) transported are inserted in the membrane
B. Glycogen synthase is stimulated
C. Glycogen phosphorylase is inhibited
D. Hexokinase is stimulated
E. Gluconeogenesis is inhibited
Which of the following is not a mechanism of drugs used to treat Type II Diabetes?
A. Stimulate breakdown of incretins
B. Block ATP-K+ channels in beta cells
C. Inhibit digestion of complex carbs in intestine
D. Stimulate PPAR gamma
E. Inhibit gluconeogenesis
Which of the following will allow you to tell whether a coma in a diabetic person was caused by
hypoglycemia due to overdose of insulin?
A. Dehydration
B. Hypotension
C. Hyperventilation
D. Pale skin, sweating
E. All of the above