Genetics and Environment in Diabetes Flashcards
Why is it hard to find genetic factors for T2D?
Because increased diabetes cases within a family, are caused by sharing the same lifestyle, habits (smoking, sedentary behaviors), diet rather than caused by genes
What are IDDM loci?
Loci associated with the autoimmune destruction of ß-cells in T1D
What are significant targets of genetic analysis regarding to T1D?
HLA alleles on IDDM-1 (chr 6)
GAD2 gene on IDDM-10 (chr 10)
Insulin gene on IDDM-2 (chr 11)
Why is the HLA allele not a significant link to T1D?
Even with high-risk haplotypes, chances to develop T1D are very low
What are the SNP that are thought to be related to T2D connected with?
Elevated serum triglycerides levels in CT, and TT genotype
CC is the wild-type
-> is not clear, bc T2D itself causes a small elevation of triglyceride
Why are environmental factors considered to contribute more to T2D prevalence?
A huge increase of prevalence of T2D in the last 15 years
genetic factors doesn’t cause a huge change in this short time
How has the environment changed?
-more chemical exposure (pesticide - grow food, preservatives in food)
-more medication (we live longer)
-Changes in eating habits
-Changes in work/study habits
How might High Fructose Corn Syrup (HFCS) contribute to increased prevalence of T2D?
Glucose from corn is converted to Fructose (alternative to table sugar (sucrose)
-Easier / cheaper to grow than sugar cane
-Fructose is sweeter than glucose
-easier to incorporate into food (liquid over crystal form of glucose)
Why is fructose problematic regarding T2D?
-It is not absorbed as well as glucose is absorbed -> uptake with GLUT 5
-GLUT 5 is present in the small intestine but low in the brain, muscles, and pancreas
-NO function on pancreatic cells
-does NOT cause the secretion of insulin
Why can fructose lead to more fat production - Lipogenesis?
Bc it is not regulated in the liver
It skips the preparation phase in GLYCOLOSIS -> where two regulatory enzymes control Glycolysis
Which enzymes regulate glycolysis?
Phosphofructokinase-1 (PFK-1) and Fructose-1,6 bisphosphatase
Path of Fructose:
Fructose produces GAP and DHAP -> same effect as glucose but unregulated
-> increase of pyruvate and Acetyl-CoA in the liver -> increased production of long chain fatty acids -> excess lipids
