56.1 Metabolic Homeostasis Flashcards
Which cellular processes occur during growth?
Hyperplasia
Hypertrophy
What hormones regulate prenatal growth?
Growth hormone (GH)
Insulin like growth factors (IGF-1 and 2)
Foetal insulin
Placental growth hormones
What determines growth?
Environment: nutrition and emotional deprivation
Genetics
When is the lifetime of a human is the most rapid period of growth?
Prenatal growth within the uterus
(CONCEPTION TO BIRTH: Weight increases x 4.4x108 Length increases x 3850)
What is foetal programming?
A concept that suggests certain events occurring during critical points of pregnancy may cause permanent effects on the foetus and the infant long after birth
What are the consequences of nutrient restriction during the fetuses time in the womb later in life?
-Increased risk of insulin resistance
-Increased risk of obesity
-Increased risk of cardiovascular disease
What are the effects of a diabetic mother on infants? Why does this occur?
INCREASED BODY WEIGHT
Materal hyperglycaemia –> fetal hyperinsulinaemia –> increased fat deposits, length and body mass
What are the consequences on the new-born of nutritional restriction in utero?
= reduction in endocrine and paracrine IGF
= resetting of foetal development to accommodate nutritionally deprived environment
= insulin, IGF and GH resistance = slower growth rate = smaller baby with reduced nutritional demands
Name two conditions which come about as a result of congenitally affected foetal growth
Leprechaunism
Pancreatic agenesis
What causes leprechaunism?
Mutation in the insulin receptor gene = severe dwarfism as a result of not being able to take up glucose (hyperglycaemia)
What is pancreatic agenesis? What are the consequences?
Anatomical variation in the pancreas characterised by a partial or total loss of the body and tail
Results in a 50% reduction in body weight
Name two foetal conditions which occur as a result of malnutrition
Marasmus (loss of adipose tissue, low blood glucose)
Kwashiorkor (oedema and altered pigmentation)
What is the result of excessive GH secretion?
Giantism
What is the result of insufficient GH secretion?
pituitary dwarfism
Which cell type makes GH?
Somatotrophs in the anterior pituitary
Which hormone triggers the release of GH from the anterior pituitary?
GH releasing hormone which acts on somatotrophs
Which hormone exerts negative feedback on GH release?
IGF-1 (as GH triggers IGF-1 secretion which mediates the actions of GH)
Somatostatin
What are the effects of GH?
Lipolysis of adipose tissue
Stimulation of gluconeogenesis
Stops glucose uptake by muscle
Opposite to insulin
When is the majority of GH released?
At night during sleep
What is acromegaly? What are the symptoms?
An excess of GH AFTER puberty
Epiphyseal plates closed up = no longitudinal growth
Thickening of bones and soft tissues of the head, hands and feet
What are the hormones involved in control of energy metabolism that are mentioned in the spec?
- IGF1 (insulin-like growth factor 1)
- IGF2 (insulin-like growth factor 2)
- Insulin
- Growth hormone
- Human placental lactogen (hPL)
Where is endocrine IGF-1 synthesised?
Liver
Where is autocrine/paracrine IGF-1 synthesised?
Muscle
Cartilage
Bone
What are the effects of IGF-1? (5)
Binds to receptor tyrosine kinase:
-Promotes uptake of amino acids
-Stimulates protein synthesis
-Stimulates glucose uptake to muscle tissue
-Inhibits apoptosis
-Promotes tissue expansion
What stimulates IGF-1 production?
Insulin (Promotes a shift to greater rates of glucose breakdown, storage and uptake to provide nutrients for cellular growth.)
Growth hormone
What is the result of pituitary dwarfism secondary to GH deficiency on IGF-1 and IGF-2 concentrations and why?
Less GH:
Decreased circulating IGF-1 which relies on GH to stimulate its synthesis and release
None/little effect on IGF-2
Where is IGF-2 produced?
Thecal and granulosa cells during folliculogenesis
How does the timing of peak concentrations of IGF-1 and 2 differ?
IGF-1 = peaks during puberty when growth is increasing (greatest growth rates observed when IGF-1 is peaking)
IGF-2 = mediates interuterine growth (peaks just before birth)
What is the function of IGF-2?
Binds to IGF1 and IGF2 receptors
-Promotes granulosa cell differentiation during follicular phase
-Promotes progestrone secretion during luteal phase (works with LH)
-Promote growth in utero
What effect does insulin, IGF1 and IGF2 all have on the body?
Hypoglycaemia
What is the result of IGF-2 knockouts?
Impaired foetal growth
reduced placenta size
What does excessive IGF-2 secretion result in?
Somatic overgrowth
How does foetal insulin regulate IGF-1?
Placental glucose transfer causes release of foetal insulin
Foetal insulin acts on maternal liver to trigger IGF-1 release
Fetus grows
What is the role of insulin?
Promotes a shift to greater rates of glucose breakdown, storage and uptake to provide nutrients for cellular growth. Induces the secretion of hepatic IGF1 for its pro-growth effects
What is the function of human placental lactogen?
Similar structure and function to growth hormone (1% as potent but present at 50X higher)
Modifies energy state of the mother to facilitate energy supply to foetus
Anti-insulin properties
-reduces maternal insulin sensitivity = increase in maternal blood glucose
-increases lipolysis of free fatty acids
-reduces maternal glucose utilisation
Which cells make hPL?
Secreted by syncytiotrophoblasts during pregnancy
What are the hormonal changes which occur during starvation?
Decreased insulin and increased glucagon secretion
What are the short term adaptations of the body to starvation?
Driven by glucagon:
-Gluconeogenesis in the liver
-Glycogenolysis
-Lipolysis and beta oxidation in adipocytes
What are the long term adaptations of the body to starvation?
Preservation of glucose for tissues which require it: red blood cells, brain and adrenal medulla
-Gluconeogenesis (muscle tissue metabolised to generate amino acids for glucose production)
-Ketogenesis (for heart and brain and renal cortex)
What are the symptoms of chronic malnutrition? (6)
Elevated ketogenesis
Hypoglycaemia
Weight loss
Stunted growth during childhood
Fatigue
Immune suppression
What are the metabolic changes that occur during chronic malnutrition?
Growth slows or stops so that protein and energy can be used for maintenance of existing tissues
Increased lipolysis (raised plasma free fatty acids)
Ketogenesis
Gluconeogenesis
Reduction in thermogenesis
What score is used to assess patients with malnutrition?
Malnutrition-inflammation score (MIS)
How does the malnutrition inflammation score assess?
Assesses 7 components in patients with chonric kidney disease:
-changes in the dry weight of dialysis products
-dietary intake (appetite)
-appearance of GI symptoms
-tiredness and functional capacity
-occurrence of comorbidities
-examined (observable) decreases in subcutaneous fat or signs of muscle wasting, accompanied with BMI decreases
-lowered serum albumin/total iron binding capacity
What do the hormones involved in energy metabolism all rely on?
NUTRITIONAL INTAKE
-amino acids and glucose trigger insulin secretion
-amino acids trigger GH secretion
-iodine required for thyroxine hormone
What will cause body mass to increase?
Energy intake exceeding energy expenditure
Which hormones are involved in the control of body weight?
LEPTIN
Hormones which regulate appetite (CCK, PYY and GLP-1)
Sex steroids (influence fat distribution to promote fat storage around the lower body = better resistance to excessive weight gain)
Where is leptin produced?
Adipose tissue at a rate which is proportional to fat content and overall mass
How does leptin regulate body weight?
Sensed by the POMC/CART neurons of the arcuate directly and via connections to the ventromedial ‘satiety’ centres of the hypothalamus
Why may adipose tissue be thought of as an endocrine organ?
It secretes a hormone leptin in proportion to fat stores (BMI)
Where are the two main places fat can be deposited?
Subcutaneously
Visceral
What is the difference in the significance of subcutaneous and visceral fat deposition?
Visceral fat is more dangerous and associated with increased metabolic diseases (insulin resistance)
Subcutaneous fat = beige tissue instead of white and incorporates brown adipocytes for thermogenesis (protection against CVD and T2DM)
Why do wild type mice paired to ob/ob mice cause ob/ob to lose weight?
High leptin secretions by wild type mouse are shared to wild type circulation resulting in a decreased feeding drive for ob/ob mouse causing it to lose weight
Why does leptin have little effect on obese individuals?
Hyperleptinemia causes leptin resistance
Which individual is more likely to have insulin resistance?
A = more visceral fat deposits than cutaneous fat
Correlates with T2DM
same BMI
What BMI does someone have to have to be qualified as obese?
30
What is the role of adipose tissue in inflammation in the development of diabetes?
Fat tissue contains 50% macrophages
When fat cells die - release inflammatory mediators which activate macrophages to engulf them
Attracts other immune cells and mount an immune response on the adipocytes
cause the fat tissue to become insulin resistant
TNF-alpha blocks insulin signalling (produced in obese patients with adipose tissue macrophages)
What are the consequences of obesity?
Decline in health:
-Increased in T2DM
-Increased atherosclerosis (increased LDLs) and CVD
-Hypertension
-Thrombosis
What is malnutrition?
Deficiencies, excesses or imbalances in a person’s intake of energy and/or nutrients.
