Lect 22

Question 1

Type I diabetes is caused by

Answer 1

• immune mediated destruction of B-cells
• absolute insulin deficiency

Question 2

peak onset of Type I diabetes

Answer 2

11-13 years

Question 3

What are the three main clinical manifestations of type I diabetes? which are induced by hyperglycemia and which is induced by insulin deficiency

Answer 3

1. polydipsia
   
   • hyperglycemia-induced: H20 is osmotically attracted from cells
2. polyuria
   
   • hyperglycemia-induced: acts as osmotic diuretic
3. polyphagia
   
   • insulin deficiency: depletion of cellular stores of fluel produces cellular starvation and increases in hunger

Question 4

type I diabetes can lead to what threatening condition

Answer 4

• diabetic ketoacidosis
  
  • insulin deficiency leads to glucagon excess -> glucagon promotes fatty acid oxidation -> excessive oxidation leads to formation of keytone bodies

Question 5

define metabolic syndrome

Answer 5

name for a group of risk factors that occur together and increase the risk for coronary artery disease, stroke, and type 2 diabetes

Question 6

Genetics + aging + obesity and inactivity can lead to

Answer 6

insulin resistance

Question 7

what conditions are associated with insulin resistance

Answer 7

• type II diabetes
• HTN
• dyslipidemia
• atherosclerosis

Question 8

type 2 diabetes ranges from what two etiologies

Answer 8

• insulin resistance
• insulin secretory defect with insulin resistance

Question 9

insulin resistance seen in type II diabetes occurs mainly in what organ

Answer 9

muscle

Question 10

insulin resistance seen in type II diabetes MOA

Answer 10

• reduction in insulin receptor content
  
  • decrease in tyrosine kinase activity
• defects in IRS-1, IRS-2 (Insulin receptor substrate)
  
  • decreased glucose transport
  • defective vesicular transport to surface membranes

Question 11

how does type II diabetes effect the liver

Answer 11

• glucose exceeds the capacity of the liver leading to increased storage of fatty acids and hepatic steatosis and nonalcoholic steatotic hepatitis

Question 12

glucose uptake in the liver is due to what transporter

Answer 12

Glut2

Question 13

how does the liver take in glucose without insulin?

Answer 13

• glucose uptake in liver is due to glut 2
• liver takes up glucose -> glycogen, gluconeogensis decreases and conversion of glucose to fat is promoted

Question 14

what are adipokines

Answer 14

proteins produced and secreted from adipose tissue

Question 15

adipokines production is increased in what condition? What can it cause?

Answer 15

• production increased with obestiy
• may contribute to a “low grade” inflammation

Question 16

List the adipokines that may be involved in the pathophysiology of obesity linked disorders

Answer 16

• Leptin
• Adiponectin

Question 17

function of leptin

Answer 17

• regulates energy intake, expenditure, and appetite

Question 18

where are leptin receptors located? what does binding signal?

Answer 18

• satiety center of the hypothalamus
• signals the brain that the body has had enough food to eat
• *thus defect in gene or signal transduction -> overeating

Question 19

expansion of adipose stores increases what hormones which functions to decrease calorie intake by inhibiting hunger and stimulating satiety

Answer 19

leptin

Question 20

leptin stimulates thermogenesis which has what effect

Answer 20

restore fat mass to setpoint

Question 21

leptin circulates at levels proportional to

Answer 21

• body fat content
  
  • in response to increases in adipose stores, higher leptin levels inhibit food intake
  • in response to decreases in adipose stores, lower leptin levels stimulate food intake

Question 22

obesity is associated with what level of leptin levels? what is the problem?

Answer 22

• higher plasma leptin level
• resistance to leptin
  
  • excess food intake not controlled by the anti-appetite effects of leptin

Question 23

Adiponectin is secreted primarly from what tissue

Answer 23

adipose tissue

Question 24

levels of Adiponectin are inversely correlated with

Answer 24

• BMI
  
  • levels are decreased in obestiy
  • weight loss and caloric restriction all increase levels

Question 25

in type I diabetics, Adiponectin levels are

Answer 25

lower, indepedent of age or BMI

Question 26

Adiponectin effects

Answer 26

• metabolism
  
  • increases glucose uptake
  • increases insulin sensitivity
  • increases fatty acid oxidation and clearance
  • suppresses gluconeogenesis

Question 27

type I diabetes have high or low pre-exercise glucose levels? why?

Answer 27

• pre-exercise glucose is high
• remains the preferred source of energy
• very little fatty acid oxidation
• glucose use is greater than hepatic glucose production

Question 28

type I diabetics don’t typically have a plasma insulin drop during exercise. What effect does this have on glucagon and hepatic glucose production?

Answer 28

• elevated insulin levels prevent the release of glucagon (exogenous insulin refers to the insulin people inject or infuse via an insulin pump)
  
  • inhibits glycogenolysis and gluconeogenesis
  • hepatic glucose production is inhibited

Question 29

therefore, type I diabetics have a greater risk of what occuring during exercise

Answer 29

• exercise induced hypoglycemia
  
  • work and high insulin levels enhance glucose uptake by the working muscle

Question 30

describe insulin shock

Answer 30

• excessive insulin in blood -> increased glucose uptake by cells -> hypoglycemia and decreased CNS function -> three things
  
  • if glucose intake, blood glucose returns to normal
  • clinical signs
  • no glucose intake, levels decrease further

Question 31

exercise has what effect on insulin sensitivity in type II diabetics

Answer 31

• increases insulin sensitivity
• increases GLUT-4
• increases glycogen synthase activity