molecular defects diabetes

Question 2

MHC Class IIType _diabetes higher in individuals with DQA301 allele or DRB1401 allele

Answer 2

1

Question 3

Twin studiesone twin gets type 1 diabetes –>30% chance the other twin will get type 1 and a 70% lifetime expectancy of __types ofdiabetes

Answer 3

all

Question 4

Insulin Resistancearises first in ____ and __ then at later stages in the liver.•The causes may be both genetic and environmental, including obesity

Answer 4

muscle and fat

Question 5

Insulin ResistanceLower output of insulin+ inability of insulin to suppress gluconeogenesis in the liver may be needed to precipitate Type _ diabetes.

Answer 5

2

Question 6

Insulin Resistance factors: Elevated_______ Inflammatory mediators High levels hormones that antagonise insulin (3) High levels of insulin

Answer 6

fatty acidsglucagon, adrenaline, glucocorticoidscan arise in obesity, metabolic syndrome and endocrine disorders e.g. Cushing’s syndrome.

Question 7

Fatty acids influence glucose uptakePlasma conc of NEFA rise in ___.• what is the M-value? •Higher values indicate good insulin sensitivity

Answer 7

obesityamount of glucose infused to maintain blood glucose levels, following infusion of insulin, to prevent hypoglycaemia

Question 8

increased insulin–> increased release of FA, liver –>TAG –> recirculated as __: (dyslipidaemia).•stimulation of some cells of the sympathetic nervous system –>____.• may increase ovarian androgen production : PCOS symptoms

Answer 8

VLDL hypertension

Question 9

Insulin response substrates (IRS)•IRS1 :main type –>metabolic effects of insulinIGF-1: works through __. secreted from the liver in response __

Answer 9

1. IRS-22. GH

Question 10

IRS1: PI3K Tyr phosphorylation__inhibition of lipolysis, glucose uptakeIRS2: Suppresses hepatic____, beta cell growth, brain growth, food intake

Answer 10

decreasedgluconeogenesisin type 2 diabetes, excess insulin degrades IRS. Tyr p decreases, Ser p increases

Question 11

Maturity Onset Diabetes of Young (MODY)•~2% of diabetes – 0.1% of population• no Islet cell __- beta cell destruction•Differences from Type-2 - age - autosomal ___inheritance -

Answer 11

antibodies dominant no association with obesity

Question 12

MODY1 : mutations in ___ cause 1% Insulin secretion normal at birth: but ↓ dramatically with age.•MODY2 Mutations in ___ affects glucose sensing in pancreas.15% Insulin secretion impaired at birth but stays ~stable.•MODY3 Mutations in __ cause 70% Insulin : same as mody1

Answer 12

1. HNF-4α2. glucokinase 3. HNF-1α

Question 13

•MODY4 : mutation: __ in β-cells involved in regulating insulin gene expression. ~ 1% of MODY.•MODY5 ___ transcription factor. ~ 1% •MODY X ~ 11%

Answer 13

4. PDX-1 Transcription Factor5. HNF 1β

Question 14

MIDD: Mitochondrial Diabetes •maternal inheritance•variable penetrance.•Accounts for 1-2% of all diabetes.•Often ____as either type-1 or type-2

Answer 14

misdiagnosed

Question 15

MIDD: Mitochondrial Diabetes •When mutant mitochondria predominate - oxidative capacity ___.•In β- cells –> ↓ capacity to secrete insulin: as insulin secretion is linked to glycolysis.•Symptoms e.g. muscle weakness, deafness, ______ and _____

Answer 15

reducedneurological problems and lactic acidosis

Question 16

Gestational Diabetes•Severe insulin resistance caused by hormonal changes and metabolic stress of pregnancy.•In women with low insulin secretory capacity •Affects 2% of pregnancies of non diabetic women.•Symptoms normally disappear after birth but 60% of these women ___________

Answer 16

go on to develop diabetes in later life.

Question 17

Other Rare Conditions Which Have Similar Symptoms to Type-2 Diabetes•_______to insulin receptor or to insulin•Mutations in insulin receptor (can cause Leprechaunism)•Glucagonomas

Answer 17

Antibodies

Question 18

Hyperthyroidism: •↑ insulin resistance and diabetes Acromegaly •60% insulin resistant and 20% diabetic.•Admin of GH __subjects ↑ insulin resistance•GH - deficient children are hypoglycaemic.

Answer 18

normal

Question 19

•Excess glucocorticoids - •↑ insulin resistance and frank Type-2 diabetes.due to IRS1 - tyrosine phosphorylation. Adrenaline ↑ insulin resistance +blocks insulin secretion.• Phaeochromocytoma –>• ↑ glycogenolysis and glucose clearance• ↓Tyr phosphorylation of IRS1.

Answer 19

1. decreases