Type I Flashcards
What is diabetes insipidus?
Absence of ADH or insensitivty of the kidneys to ADH
Why is Type1 heavily associated with the histocompatibility complex (MHC)?
HLA DR3/4 has the highest risk, one allele of MHC class II type 3 and allele of type 4. These are degraded by antigen presenting cells
Where is the loci of type 1 susceptibility?
chromosome 11
CTLA-4, function
peripheral self-tolerance
T cell activation through Tcell receptor and CD28 leads to higher expression of CTLA-4, inhibitory receptor
Zinc’s significance?
packages insulin into a hexamer, this is how insulin is stored in secretory granules
What is the glucose tolerance test?
1 Fasting
2 Drinks
How is blood filtrated?
Renal tubule associated with 2 capillary beds, glomerus and peritubular.
Blood passes through glomerus. walls of glomerus contain holes.
Water and solutes are squeezed out of the capillaries into the bowmans capsule.
red blood cells and proteins cant pass holes normally
What are the blood Glc levels of diabetic patients?
25mM instead of 4-9mM
Why cant Type 1 diabetic patients underdo glycogen synthesis in the absence of insulin?
Glycogen synthase is kept in a phosphorylated, inactive form. Hence type 1 diabetics can become hypoglycaemic
Why is glycogen breakdown promoted on type 1?
Insulin activates protein phosphatase I (PPI), leading to dephosphorylation and inactivation of glycogen phosphorylase.
With no insulin, glycogen phosphorylase remains activae, allowing glycogen breakdown.
Why is Glycolysis inhibited in type 1?
By the increase of gluconeogenesis through PFK2.
PFK2 is regulated by phosphorylation .
High blood glc = active PFK2
What is the first glucose attatched to?
Tyr 194 of glycogenin
What is Von Gierke’s disease?
Type1a:
Caused by a mutation in G6Pase of the LIVER, intestinal mucosa and kidney
G6P cannot be hydrolyzed to glucose.
G6P buildup inhibits glycogen breakdown.
Glycogen builds up (hepotomegaly)
Type1b:
Defect in microsomal G6P translocase in the LIVER
Similar effects to 1a
Type1c:
Defect in microsomal Pi transporter in the LIVER
similar to 1a
What is Pompe’s disease?
autosomal recessive
Type II glycogen storage disease.
Lack of lysosomal enzyme, acid a glucosidase (acid maltase) which breaks 1-4 a bonds
Lysosomes gets filled full of glycogen and cant work
What is Cori’s/Forbe#s disease?
Type IIIa
Defect in debranching enzyme in liver, skeletal and cardiac muscle
Glycogen accumilates because only the outer branches can be removed by phosphorylase
Same as 1a Von Gierke but milder as some glucose is released
