L77: Metabolic Homeostasis Flashcards

(37 cards)

1
Q

What happens in starvation?

A

Brain needs constant supply of glucose (180g /day) -> break down fat stores, liver glycogen, and proteins)

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2
Q

What happens in a prolonged fast?

A

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

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3
Q

What is obesity?

A

BMI>30

Waist-Hip ratio greater than 0.95M or 0.85W

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4
Q

What is metabolic syndrome?

A

visceral obesity
insulin resistance
dyslipidemia
HTN

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5
Q

What is the primary hormone produced by white adipose tissue?

A

Leptin

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6
Q

What is SREBP-1C?

A

Sterol REgulatory Binding Protein 1C
Promotes TG synthesis
Activated by lipids and insulin

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7
Q

What is PPARy?

A

Peroxisome Proliferator activated Receptor Gamma
Nuclear steroid hormone receptor
Regulates TG storage and adipocyte differentiation

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8
Q

What is a PPARy agonist used clinically?

A

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)

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9
Q

What is the relationship between leptin and fat levels?

A

Higher body fat-> increased levels of leptin

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10
Q

What does leptin do?

A

inhibit appetite and food intake

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11
Q

Why do obese people have high levels of leptin?

A

Potentially insensitive to leptin effects -> very high levesl

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12
Q

What hypothalamic hormones stimulate appetite? What does leptin do to these?

A
Neuropeptide Y (Arcuate  nucleus)
AGRP (Paraventricular Nucleus)

Leptin inhibits these to decrease food intake

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13
Q

What hypothalamic hormones inhibit appetite? What does leptin do to these?

A

aMSH (Paraventricular Nucleus)
CART (Arcuate Nucleus)

Leptin stimulates these to decrease food intake

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14
Q

What happens in insulin resistance?

A

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

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15
Q

What causes a conversion from Type II to Type I DM?

A

Beta cell depletion/exhaustion

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16
Q

What is T2DM?

A

Diabetes Mellitus Type II: impaired beta cell funciton as well as insulin resistance

17
Q

What does HbA1C measure?

A

Measures average blood glucose concentrations over a long period of time as glucose increases the number of glycosylated RBCs

> 6.5% = diabetes

18
Q

Whats diabetic/normal levels of fasting blood glucose?

A
126+ = T2DM
100-125= prediabetes
19
Q

What are sx of T2DM?

A

Polyphagia
Polyuria- excess glucsoe in blood -> inc plasma osmolarity -> excessive water and sodium loss
Polydipsia

20
Q

What are Tx options for T2DM?

A

Sulfonylureas(glipizide)
Biguanides (Metformin)
a-glucosidase inhibitors

21
Q

What does sulfonylureas do to treat T2DM?

A

Close ATP dependent K+ channels in beta cells -> insulin release

22
Q

What does metformin do to treat T2DM?

A

Inhibit hepatic gluconeogenesis

Increase insulin receptor activiyt -> more sensitive to insulin -> inc glucose uptake

23
Q

What does a-glucosidase inhibitors do to treat T2DM?

A

Delays intestinal absorption of carbs

24
Q

What can cause bet cell dysfunciton oin T2DM?

A
Islet amyloid buildup
ER stress
Lipotoxicity
Glucose toxicity
Incretin hormone dysregulation
Islet inflammation
25
What characterizes T1DM?
Insulin-Dependent Diabetes Development of ketoacidosis without insulin therapy Juvenile onset
26
What causes T1DM?
Destruction of pancreatic beta cells -> insulin dependent
27
What is used to treat T1DM?
Insulin injections, diet, monitor blood glucose
28
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)
29
What causes diabetic coma?
Severe dehydration and metabolic acidosis
30
What are the counterregulatory hormones to insulin?
Glucaon, GH, cortisol, catecholeamines
31
What causes diuresis and dehydration in diabetics?
Increased plasma glucose levels -> inc blood osmolality
32
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
33
When does islet neogenesis occur?
During embryonic development
34
When does beta cell replication occur?
During childhood/adolescence but stable in adults
35
What is PDX1?
important for islet neogenesis and beta cell proliferation
36
What is TCF72?
Downstream targets regulate beta cell proliferation
37
What does Exenatide do?
``` Incretin Mimetic (GLP-1 agonist) REstores 1st phase insulin secretion in T2DM patients and improved 2nd phase insulin secretion ```