Diabetes Flashcards
Pancreatic cells
alpha -________
Beta - ________
Delta - _____
Islet Cell - alpha in the middle and beta around
Alpha = glucagon
Beta = insulin
Delta = somatostatin
Mnemonic for causes of pancreatitis
I GET SMASHED
I: idiopathic
G: gallstone; common bile duct/obstruct Ampulla of Vater —> obstruction- backflow causes lysis of pancreatic cells – pancreatitis
E: ethanol (-OH)
S: steroids
M: mumps (paramyxovirus) EBV CMV
A: Autoimmune as PAN & SLE
S: Scorpion sting – tityus trinitatis-trinidad/ snake bite
H: hypercalcemia, hyperlipidemia, hypertriglyceridemia and hypothermia
E: ERCP (endocopic retrograde cholangio pancreatography)
D: drugs (SAND-steriods & sulfonamindes, azathioprine, NSAIDS, diuretics, duodenal ulcers)
Overall action of insulin
A- Promotes synthesis of energy reserve —> anabolic action
B- Released by B-cell due to increased glucose in the blood
C- Inhibit carbohydrate degredation
G- Inhibit gluconeogenesis
U- Stimulates uptake of glu, aa, FFA into cells, reduces concentration in blood
Action of insulin in adipose
put glu in, stop fat breakdown and increase fat production
Increase glucose uptake
Increase Lipogenesis
Reduced Lipolysis
Insulin action on liver
glycogen (Sugar storage), increase fat production, reduce sugar production
Increase glycogen synthesis
Increase lipogenesis
Reduce gluconeogenesis
Insulin action on striated muscle
Take up glu, make glycogen (sugar storage) and protein
Glucose uptake
Glycogen synthesis
Protein synthesis
Counter-hormones to insulin
GAC
Glucagon (liver only)
Adrenaline (liver and muscle)
Cortisol
Muscle = increase proteolysis
Adipose = increase lipolysis
FFA for energy
T2D basic pathway
Genetic predisposition + obesity lifestyle factors —> insulin resistance —> compensatory B cell hyperplasia (Normoglycemia) —> B cell failure (impaired glu tolerance) —> B-cell fail (Diabetes)
Cause of Insulin resistance
Increased hepatic glu production
Reduced peripheral glu uptake and utilisation
Dyslipidemia
All increase demand for insulin
IR = hyperglycemia + hypertriglyceridermia
Insulin resistance to T2D
Initially increase demand = increase size
In susceptible B cell w/ genetic risk = failure for B cell to compensate and increased glu and FFA —> glucolipotoxicity
Beta cell dysfunction and growth genes
HNF1a HNF4a Kir6.2 TCF7L2 Mitocondrial
Insulin receptor is a type of
Tyrosine kinase
Rapid and long-term role of insulin signalling
Rapid = glu uptake via GLUT 4 translocation, enzyme activation
Long term = enzyme synthesis, cell growth
Termination of Insulin receptor signalling
Protein phosphatases like PTEN and PTPN1 dephosphorylate residue on the receptor or downstream kinases
-Ive feedback of insulin signalling is modulated by
IRS protein on Ser residue terminates Insulin signalling
IRS protein on Ser residue is phosphorylated by downstream kinases in insulin pathway.
IRS detaches from receptor and changes docking of signalling protein + its degredation —> terminates insulin action
Cause of hyperlipidemia in diabetes
Excess glu in liver (GLUT2)
Glu in liver turns to TG by increased hepatic de novo lipogenesis
Effects on IR on lipid metabolism and liver
Overall increased FFA and TG
- increased lipolysis and reduced Fat storage = increase FFA
- Reduced VLDL and cylomicron clearance due to reduced LPL activity = increase TG
- In liver excess TG production
—> fatty liver
Diabetes is defined by
Insulin deficiency
Glucagon excess
Role of glu on glucagon
Normally Glu reduced glucagon release
Alpha cell still release glucagon
Role of GLP-1 in insulin secretion
GLP-1 = from gastrointestine
- Acts on GLP-1 receptor on B-cell to increase glu dependant insulin release via ACh, MR and cAMP
- Suppress Glucagon release
Impact of high Glu
High glu but blocked from going into cell
- Cell uses FFA oxidation to produce Ketone body —> acidosis
- Glucouria —> polyuria —> dehydration —> polydypsia
Metabolic syndrome in IR- what causes the inflammatory state in insulin resistance
Excess energy —> adipose = hypertrophy and hyperplasia , vascular doesn’t keep up —> necrosis, apoptosis and pro-inflammatory response
Kinases inhibiting Insulin’s action
JNK
IKKb
Release of kinase inhibiting action of insulin is mediated by
- Hyperlipidemia and hyperglycemia causing mitocondrial dysfunction and oxidative stress
- Necrotic debris, inflammation and saturated fatty acids activating kinases
