Metabolic homeostasis (L11)

Question 1

Seven causes of wasting

Answer 1

Trauma
Infection
Burns
Malnutrition/starvation
Cancer
Psychological
Drug abuse

Question 2

Daily brain glucose requirement

Answer 2

180g

Question 3

Initial source of glucose during starvation

Answer 3

Endogenous fatty acid lipolysis (80%), protein degradation, and breakdown of liver glycogen

Question 4

Metabolic switch

Answer 4

Ketone bodies are used for brain energy supply

Question 5

How much protein is broken down in prolonged fasted state?

Answer 5

Only 20g/day

Question 6

Waist-hip ratios with increased cardiovascular problems

Answer 6

Greater than 0.95 for men, greater than 0.85 for women

Question 7

Metabolic syndrome

Answer 7

Presence of visceral obesity, hypertension, insulin resistance, and dyslipidemia

Question 8

Parameters for metabolic syndrome

Answer 8

BP > 135/80
HDL 150 mg/dL
Waist > 40 in (men) or 35 in (women)
Fasting glucose > 100 mg/dL

Question 9

Primary hormone in white adipose tissue

Answer 9

Leptin

Question 10

Important transcription factors for leptin

Answer 10

SREBP-1 and PPAR-gamma

Question 11

What does SREBP-1 do?

Answer 11

Promotes triglyceride synthesis

Question 12

What does PPAR-gamma do?

Answer 12

Regulates triglyceride storage and adipocyte differentiation

Question 13

PPAR-gamma agonists

Answer 13

Thiazoladinediones; help in treatment of insulin resistance

Question 14

Side effect of PPAR-gamma agonists

Answer 14

Weight gain - clinical consideration

Question 15

Relationship between total fat and leptin concentrations

Answer 15

More body fat correlates with higher leptin levels, but cells become resistant to its effects

Question 16

Hypothalamic stimulators of appetite

Answer 16

Neuropeptide Y, agouti-related protein,

Question 17

Hypothalamic inhibitors of appetite

Answer 17

alpha-MSH, cocaine-amphetamine related transcript (CART)

Question 18

Process of insulin resistance

Answer 18

Slow; constant high levels of blood insulin levels will downregulate the number of insulin receptors and eventually less insulin is made

Question 19

Conversion of type I diabetes to type II diabetes

Answer 19

Beta cell “exhaustion” that leads to complete lack of insulin production

Question 20

Elevated HbA1C in diabetics

Answer 20

> 6.5%

Question 21

Fasting glucose in diabetes vs prediabetes

Answer 21

100-125: prediabetic

126+: diabetic

Question 22

Oral glucose tolerance test

Answer 22

Glucose measured after an 8 hour fast, then 2 hours after a 75g consumption of glucose

Question 23

Parameters of oral glucose tolerance test

Answer 23

140-199 mg/dL: prediabetic

200+: diabetic

Question 24

Symptoms of DMII

Answer 24

Polyphagia, polydipsia, and polyuria

Question 25

Biguanides

Answer 25

Metformin: inhibits hepatic gluconeogenesis, increases insulin receptor activity, making cells more sensitive to insulin

Question 26

Alpha-glucosidase inhibitors

Answer 26

Delays intestinal absorption of carbohydrates

Question 27

Proposed mechanism of beta cell dysfunction in DMII (7)

Answer 27

``` Glucose/lipid toxicity Amyloid buildup ER stress Oxidative stress Reduced expression of beta cell genes Decreased incretins Islet inflammation ```

Question 28

Diabetes mellitus type I

Answer 28

Characterized by a juvenile onset and ketoacidosis in the absence of insulin treatment.

Question 29

Prevalence of DMI

Answer 29

2-5% of diabetes cases

Question 30

Etiology of ketoacidosis

Answer 30

Lack of insulin and increased counterregulatory hormones, increasing fatty acid oxidation and acidosis

Question 31

What happens if ketoacidosis is not treated?

Answer 31

Results in acidosis, severe dehydration, and diabetic coma

Question 32

Complications of DM

Answer 32

Renal failure

Question 33

Partial vs. absolute insulin deficiency

Answer 33

In the presence of some insulin, there will be no ketone formation; only occurs in the complete lack of insulin

Question 34

Plasma osmolality in relationship to mental state

Answer 34

Severe dehydration that accompanies a hyperglycemic hyperosmotic state will result in altered mental status

Question 35

Risk factors for DMII

Answer 35

Genetic predisposition and environment

Question 36

Gene actions affected in genetic predisposition for DMII

Answer 36

Most affect proliferation/differentiation/survival of beta cells, but some affect insulin signaling, glucose transport, or obesity

Question 37

Genes affected in DMII

Answer 37

TCF72: Wnt pathway, coactivator of beta-catenin

Question 38

What are the two environmental factors that predispose to DMII development?

Answer 38

Impaired beta-cell proliferation during childhood; increased propensity for insulin resistance

Question 39

What factors during childhood will predispose to DMII?

Answer 39

Maternal factors during pregnancy; malnutrition

Question 40

Key early characteristic for DMII

Answer 40

Impaired rapid release of insulin

Question 41

Islet cell development

Answer 41

Islet neogenesis: embryonic devlopment | Beta cell proliferation continues throughout childhood, but is stable in adults

Question 42

Genes important in islet cell development

Answer 42

PDX-1: islet cell differentiation and beta cell proliferation TCF72: downstreat targets regulate beta cell proliferation

Question 43

Exenatide

Answer 43

GLP-1 agonist: incretin mimetic that helps improve second phase insulin release

Question 44

Clinical considerations for exenatide

Answer 44

May cause pancreatic toxicity (2013)