L77: Metabolic Homeostasis Flashcards
What happens in starvation?
Brain needs constant supply of glucose (180g /day) -> break down fat stores, liver glycogen, and proteins)
What happens in a prolonged fast?
Dominant catabolic state
Metabolic Switch: brain uses ketone bodies rather than glucose for energy -> decrease reliance on glucose as fuel source
Protein breakdown continues but much lower rate
What is obesity?
BMI>30
Waist-Hip ratio greater than 0.95M or 0.85W
What is metabolic syndrome?
visceral obesity
insulin resistance
dyslipidemia
HTN
What is the primary hormone produced by white adipose tissue?
Leptin
What is SREBP-1C?
Sterol REgulatory Binding Protein 1C
Promotes TG synthesis
Activated by lipids and insulin
What is PPARy?
Peroxisome Proliferator activated Receptor Gamma
Nuclear steroid hormone receptor
Regulates TG storage and adipocyte differentiation
What is a PPARy agonist used clinically?
TZD: PPARy agonist used to treat insulin resistance in DM TII
Induces differentiation of adipocytes -> more fat cells
Increased fat storage
Side effect: Weight gain (not desirable for diabetics)
What is the relationship between leptin and fat levels?
Higher body fat-> increased levels of leptin
What does leptin do?
inhibit appetite and food intake
Why do obese people have high levels of leptin?
Potentially insensitive to leptin effects -> very high levesl
What hypothalamic hormones stimulate appetite? What does leptin do to these?
Neuropeptide Y (Arcuate nucleus) AGRP (Paraventricular Nucleus)
Leptin inhibits these to decrease food intake
What hypothalamic hormones inhibit appetite? What does leptin do to these?
aMSH (Paraventricular Nucleus)
CART (Arcuate Nucleus)
Leptin stimulates these to decrease food intake
What happens in insulin resistance?
insulin does not effectively transport glucose into cell -> glucose levels high -> hyperinsulinemia -> down reg insulin receptors (takes time, gradual)
Eventually pancreas reduces insulin output -> DM
What causes a conversion from Type II to Type I DM?
Beta cell depletion/exhaustion
What is T2DM?
Diabetes Mellitus Type II: impaired beta cell funciton as well as insulin resistance
What does HbA1C measure?
Measures average blood glucose concentrations over a long period of time as glucose increases the number of glycosylated RBCs
> 6.5% = diabetes
Whats diabetic/normal levels of fasting blood glucose?
126+ = T2DM 100-125= prediabetes
What are sx of T2DM?
Polyphagia
Polyuria- excess glucsoe in blood -> inc plasma osmolarity -> excessive water and sodium loss
Polydipsia
What are Tx options for T2DM?
Sulfonylureas(glipizide)
Biguanides (Metformin)
a-glucosidase inhibitors
What does sulfonylureas do to treat T2DM?
Close ATP dependent K+ channels in beta cells -> insulin release
What does metformin do to treat T2DM?
Inhibit hepatic gluconeogenesis
Increase insulin receptor activiyt -> more sensitive to insulin -> inc glucose uptake
What does a-glucosidase inhibitors do to treat T2DM?
Delays intestinal absorption of carbs
What can cause bet cell dysfunciton oin T2DM?
Islet amyloid buildup ER stress Lipotoxicity Glucose toxicity Incretin hormone dysregulation Islet inflammation
What characterizes T1DM?
Insulin-Dependent Diabetes
Development of ketoacidosis without insulin therapy
Juvenile onset
What causes T1DM?
Destruction of pancreatic beta cells -> insulin dependent
What is used to treat T1DM?
Insulin injections, diet, monitor blood glucose
What causes diabetic ketoacidosis?
T1DM: Decreased insulin + inc counter hormones -> increased FFA released -> inc ketone acid formation -> metabolism of ketone bodies -> inc blood acidity (dec pH)
What causes diabetic coma?
Severe dehydration and metabolic acidosis
What are the counterregulatory hormones to insulin?
Glucaon, GH, cortisol, catecholeamines
What causes diuresis and dehydration in diabetics?
Increased plasma glucose levels -> inc blood osmolality
How are plasma osmolality and mental status related?
Inc plasma osmolality -> severe dehydration-> increased altered mental status
Seen in T1 and T2DM due to hyperosmotic hyperglycemic states
When does islet neogenesis occur?
During embryonic development
When does beta cell replication occur?
During childhood/adolescence but stable in adults
What is PDX1?
important for islet neogenesis and beta cell proliferation
What is TCF72?
Downstream targets regulate beta cell proliferation
What does Exenatide do?
Incretin Mimetic (GLP-1 agonist) REstores 1st phase insulin secretion in T2DM patients and improved 2nd phase insulin secretion
