-
insulin secretion
- BGL>5M sensed by GLUT2 and glucokinase in beta cells
- increased ATP inhibits ATP sensitive K channels causing depolarisation
- voltage gated Ca channels activated releasing insulin vesicles
-
insulin MOA
- binds to tyrosine kinase receptors on target cells
- autophosphorylation triggers phosphorylation cascade of insulin receptor substrate proteins (IRS proteins)
- alterations of gene expression tending towards anabolism over catabolism
-
insulin effects on glucose handling
increased expression of GLUT4 receptors on the membranes of adipocytes, myocytes increases glucose uptake and therefore flux through glycolysis and TCA resulting in increased intracellular ATP
-
insulin effects on glycogen stores
- dephosphorylation and subsequent activation of glycogen synthase
- phosphorylation and subsequent inhibition of glucose 6 phosphorylase
- tendency towards glycogen synthesis rather than breakdown
-
insulin effects on lipid metabolism
- activates SREBP transcription factors which increase gene expression of lipogenesis enzymes such as ACC (rate limiting step in lipogenesis, conversion of acetyl coA to malonyl coA), HMGcoA
- increased malonyl coA inhibits carnitine transferase which is the transporter for FFA into the mitochondria for b oxidation, reducing ATP formation from FFA oxidation
- inhibition of HSL which causes lipolysis in adipose tissue, preventing FFA release
- activation of LPL which allows uptake of FFA from chylomicrons and VLDL in the blood
-
insulin effects on gluconeogenesis
- inhibits expression of gluconeogenesis enzymes which promote conversion of pyruvate and its tribituaries into glucose
- pyruvate carboxylase: pyruvate->oxaloacetate
- PEPCK: oxaloacetate->P-enol pyruvate
- fructose-1,6-bisphosphatase
- glucose-6-phosphatase
- also promotes conversion of pyruvate to acetylcoA for lipogenesis, glycogenesis
-
glucagon secretion and MOA
- BGL<2.5M sensed by alpha cells secretes glucagon which acts on adipocytes and hepatocytes (not myocytes) via GPCR changing the phosphorylation status of enzymes
- tendency towards catabolism over anabolism
-
glucagon effects on lipid metabolism
- activates HSL promoting lipolysis forming FFA for release into blood
- inhibits LPL reducing FFA uptake by adipocytes and hepatocytes
- decreased intracellular ATP activates AMPK which inhibits lipogenesis genes via SREBP, ACC inhibition
- reduced malonyl coA disinhibits carnitine transferase allowing FFA to enter mitochondria for b oxidation
-
glucagon effects on glucose handling
phosphorylation of glycogen synthase (deactivated) and glucose 6 phosphorylase (activated) promotes glycogen breakdown
-
metabolic syndrome criteria
- BAD WIFE
- Blood pressure high
- Albuminuria > 30mg/g
- Dyslipidemia
- Waist to hip ratio > 0.9
- Impaired glucose tolerance (not back to baseline by 2hr)
- Fasting BGL > 6
- Excess BMI >25
-
pathological processes caused by obesity
- increased oxidative stress
- proinflammatory cytokines
- hyperuricemia
- endothelial dysfx
-
consequences of obesity
- metabolic: dyslipidemia, insulin resistance
- mechanical: osteoarthritis, obstructive sleep apnea, asthma
- cancers: breast, endometrial, prostate, kidney, pancreas, colon
- cardiovascular: atherosclerosis, HTN, IHD, CVA, PVD
- psychological problems
-
fructose as a candidate environmental factor for obesity
- Too BAD
- temporal correlation
- biological plausability
- association found in cross sectional cohort studies
- direct influence in RCT
-
risk factors for childhood obesity
- PI>Maori>Asian>Euro
- SSB
- fast food availability
- TV: esp w food, exposure to advertising, sleep deprivation
- sleep deprivation: more opportunities to eat, change in thermoregulation, fatigue
- sedentary
-
endocrine signals altering intake
- insulin
- PYY
- CKK
- GLP-1
- leptin
- ghrelin (only one that increases intake)
-
endocrine signals altering metabolic activity
- neuropeptide Y: anabolic
- oxytocin/serotonin: catabolic
-
six A's of dietary counselling (or any counselling tbh..)
- Assess risk factors
- Agree on goals
- Advise on behavioural changes
- Assist to make changes and achieve goals
- Arrange for followups
- Awareness of barriers
-
hyperglycaemia symptoms
- polyuria/nocturia
- polydipsia
- polyphagia
- fatigue
- hyperventilation (acidosis)
-
diabetic ketoacidosis symptoms
- acetone breath
- NV
- polyuria/polydipsia
- hyperventilation
- blurred vision
- abdo pain
- sweating
- tremor/seizures
- coma
-
hypoglycaemia symptoms
- initially: irritability, headache, tiredness
- adrenergic: palpitations, tremor, anxiety
- cholinergic: sweating, hunger, parasthesiae
- neuroglycopenic: confusion, drowsiness, fatigue, weakness, visual changes, seizures, coma
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