Metabolic homeostasis (L11) Flashcards
Seven causes of wasting
Trauma Infection Burns Malnutrition/starvation Cancer Psychological Drug abuse
Daily brain glucose requirement
180g
Initial source of glucose during starvation
Endogenous fatty acid lipolysis (80%), protein degradation, and breakdown of liver glycogen
Metabolic switch
Ketone bodies are used for brain energy supply
How much protein is broken down in prolonged fasted state?
Only 20g/day
Waist-hip ratios with increased cardiovascular problems
Greater than 0.95 for men, greater than 0.85 for women
Metabolic syndrome
Presence of visceral obesity, hypertension, insulin resistance, and dyslipidemia
Parameters for metabolic syndrome
BP > 135/80
HDL 150 mg/dL
Waist > 40 in (men) or 35 in (women)
Fasting glucose > 100 mg/dL
Primary hormone in white adipose tissue
Leptin
Important transcription factors for leptin
SREBP-1 and PPAR-gamma
What does SREBP-1 do?
Promotes triglyceride synthesis
What does PPAR-gamma do?
Regulates triglyceride storage and adipocyte differentiation
PPAR-gamma agonists
Thiazoladinediones; help in treatment of insulin resistance
Side effect of PPAR-gamma agonists
Weight gain - clinical consideration
Relationship between total fat and leptin concentrations
More body fat correlates with higher leptin levels, but cells become resistant to its effects
Hypothalamic stimulators of appetite
Neuropeptide Y, agouti-related protein,
Hypothalamic inhibitors of appetite
alpha-MSH, cocaine-amphetamine related transcript (CART)
Process of insulin resistance
Slow; constant high levels of blood insulin levels will downregulate the number of insulin receptors and eventually less insulin is made
Conversion of type I diabetes to type II diabetes
Beta cell “exhaustion” that leads to complete lack of insulin production
Elevated HbA1C in diabetics
> 6.5%
Fasting glucose in diabetes vs prediabetes
100-125: prediabetic
126+: diabetic
Oral glucose tolerance test
Glucose measured after an 8 hour fast, then 2 hours after a 75g consumption of glucose
Parameters of oral glucose tolerance test
140-199 mg/dL: prediabetic
200+: diabetic
Symptoms of DMII
Polyphagia, polydipsia, and polyuria
Biguanides
Metformin: inhibits hepatic gluconeogenesis, increases insulin receptor activity, making cells more sensitive to insulin
Alpha-glucosidase inhibitors
Delays intestinal absorption of carbohydrates
Proposed mechanism of beta cell dysfunction in DMII (7)
Glucose/lipid toxicity Amyloid buildup ER stress Oxidative stress Reduced expression of beta cell genes Decreased incretins Islet inflammation
Diabetes mellitus type I
Characterized by a juvenile onset and ketoacidosis in the absence of insulin treatment.
Prevalence of DMI
2-5% of diabetes cases
Etiology of ketoacidosis
Lack of insulin and increased counterregulatory hormones, increasing fatty acid oxidation and acidosis
What happens if ketoacidosis is not treated?
Results in acidosis, severe dehydration, and diabetic coma
Complications of DM
Renal failure
Partial vs. absolute insulin deficiency
In the presence of some insulin, there will be no ketone formation; only occurs in the complete lack of insulin
Plasma osmolality in relationship to mental state
Severe dehydration that accompanies a hyperglycemic hyperosmotic state will result in altered mental status
Risk factors for DMII
Genetic predisposition and environment
Gene actions affected in genetic predisposition for DMII
Most affect proliferation/differentiation/survival of beta cells, but some affect insulin signaling, glucose transport, or obesity
Genes affected in DMII
TCF72: Wnt pathway, coactivator of beta-catenin
What are the two environmental factors that predispose to DMII development?
Impaired beta-cell proliferation during childhood; increased propensity for insulin resistance
What factors during childhood will predispose to DMII?
Maternal factors during pregnancy; malnutrition
Key early characteristic for DMII
Impaired rapid release of insulin
Islet cell development
Islet neogenesis: embryonic devlopment
Beta cell proliferation continues throughout childhood, but is stable in adults
Genes important in islet cell development
PDX-1: islet cell differentiation and beta cell proliferation
TCF72: downstreat targets regulate beta cell proliferation
Exenatide
GLP-1 agonist: incretin mimetic that helps improve second phase insulin release
Clinical considerations for exenatide
May cause pancreatic toxicity (2013)