Lect 22 Flashcards
Type I diabetes is caused by
- immune mediated destruction of B-cells
- absolute insulin deficiency
peak onset of Type I diabetes
11-13 years
What are the three main clinical manifestations of type I diabetes? which are induced by hyperglycemia and which is induced by insulin deficiency
- polydipsia
- hyperglycemia-induced: H20 is osmotically attracted from cells
- polyuria
- hyperglycemia-induced: acts as osmotic diuretic
- polyphagia
- insulin deficiency: depletion of cellular stores of fluel produces cellular starvation and increases in hunger
type I diabetes can lead to what threatening condition
- diabetic ketoacidosis
- insulin deficiency leads to glucagon excess -> glucagon promotes fatty acid oxidation -> excessive oxidation leads to formation of keytone bodies
define metabolic syndrome
name for a group of risk factors that occur together and increase the risk for coronary artery disease, stroke, and type 2 diabetes
Genetics + aging + obesity and inactivity can lead to
insulin resistance
what conditions are associated with insulin resistance
- type II diabetes
- HTN
- dyslipidemia
- atherosclerosis
type 2 diabetes ranges from what two etiologies
- insulin resistance
- insulin secretory defect with insulin resistance
insulin resistance seen in type II diabetes occurs mainly in what organ
muscle
insulin resistance seen in type II diabetes MOA
- 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
how does type II diabetes effect the liver
- glucose exceeds the capacity of the liver leading to increased storage of fatty acids and hepatic steatosis and nonalcoholic steatotic hepatitis
glucose uptake in the liver is due to what transporter
Glut2
how does the liver take in glucose without insulin?
- glucose uptake in liver is due to glut 2
- liver takes up glucose -> glycogen, gluconeogensis decreases and conversion of glucose to fat is promoted
what are adipokines
proteins produced and secreted from adipose tissue
adipokines production is increased in what condition? What can it cause?
- production increased with obestiy
- may contribute to a “low grade” inflammation
List the adipokines that may be involved in the pathophysiology of obesity linked disorders
- Leptin
- Adiponectin
function of leptin
- regulates energy intake, expenditure, and appetite
where are leptin receptors located? what does binding signal?
- 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
expansion of adipose stores increases what hormones which functions to decrease calorie intake by inhibiting hunger and stimulating satiety
leptin
leptin stimulates thermogenesis which has what effect
restore fat mass to setpoint
leptin circulates at levels proportional to
- 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
obesity is associated with what level of leptin levels? what is the problem?
- higher plasma leptin level
- resistance to leptin
- excess food intake not controlled by the anti-appetite effects of leptin
Adiponectin is secreted primarly from what tissue
adipose tissue
levels of Adiponectin are inversely correlated with
- BMI
- levels are decreased in obestiy
- weight loss and caloric restriction all increase levels
in type I diabetics, Adiponectin levels are
lower, indepedent of age or BMI
Adiponectin effects
- metabolism
- increases glucose uptake
- increases insulin sensitivity
- increases fatty acid oxidation and clearance
- suppresses gluconeogenesis
type I diabetes have high or low pre-exercise glucose levels? why?
- pre-exercise glucose is high
- remains the preferred source of energy
- very little fatty acid oxidation
- glucose use is greater than hepatic glucose production
type I diabetics don’t typically have a plasma insulin drop during exercise. What effect does this have on glucagon and hepatic glucose production?
- 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
therefore, type I diabetics have a greater risk of what occuring during exercise
- exercise induced hypoglycemia
- work and high insulin levels enhance glucose uptake by the working muscle
describe insulin shock
- 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
exercise has what effect on insulin sensitivity in type II diabetics
- increases insulin sensitivity
- increases GLUT-4
- increases glycogen synthase activity
