Biochemistry of T1D Flashcards
What is the issue with T1D?
The cells in the pancreas produce little or no insulin, bc they get destroyed due to autoimmune disease
-> daily insulin required
What are the symtoms of T1D?
Symptoms develop quickly, often in young people
-Frequent urination, excessive thirst, extreme hunger
-extreme fatigue, blurred vision, sudden weight loss, irritably (angry)
T1D vs T2D:
T1D: may benefit from diet change but they will always need medication
-no or less insulin produced
T2D: not fully understood
-Insulin is there but is not working properly
-insulin receptors not shaped normally
-not all the glucose transporter are open
Which cells in the Islet cells are predominant?
ß- cells: release Insulin
How is the insulin secretion in the pancreas stimulated?
how is it different from liver cells?
-Pancreas: by glucose uptake -> INSULIN secretion
-Liver cells: have insulin receptors and bind insulin -> GLUCOSE uptake
How does Insulin secretion work -> Pathway:
GLUCOSE enters the cell -> undergoes GLYCOLYSIS to produce ATP through the Krebs cycle and oxidative phosphorylation
-ATP is used to shuts down the K+ channel -> which causes depolarization of the cell membrane opening up the Ca channel -> Ca influx causes Insulin secretion
How can drugs in patients with heart disease be affected by Calcium channel blockers?
Ca channel blockers are present on the surface of myocytes -> taking too much can affect pancreatic cells and block insulin secretion -> High blood sugar
What does the structure of Insulin look like?
-Preproinsulin with 3 subunits
-Proinsulin -> Signal sequence cleaved and disulfide bonds formed
-INSULIN: C-peptide removed
Subunits left: A and B
Why is insulin not produced properly in T1D patients?
-It is believed that viral infections can cause lymphocytes to develop in the pancreas and attack and destroy ß-cells
-Assumption of genetic component: HLA-gene (responsible for recognizing foreign substances) allowing lymphocytes to develop (not a good proof for T1D)
What is the immune system targeting in the beta cells?
-Glutamic Acid Decarboxylase (GAD) recognized in 80% of T1D cases
-> Enzyme responsible for metabolizing glutamate to GABA (neurotransmitter)
What is the immune system targeting in the beta cells?
-Glutamic Acid Decarboxylase (GAD) recognized in 80% of T1D cases
-> Enzyme responsible for metabolizing glutamate into GABA, a Neurotransmitter (not known why GAD is attacked)
What is the consequence of the attack on GAD in pancreatic cells?
-immune system recognizes GAD as ‘foreign’, then
several anti‐GAD antibodies will be formed
-Antibodies attack beta cells and lyse them + they don’t regenerate -> Life long disease
What are the metabolic responses AFTER a meal that doesn’t work in diabetes patients?
-Gluconeogenesis: turned ON bc no insulin response that there is enough Glucose
-Glycogen synthesis: OFF bc there is no Glucose to make Glycogen
-Glucose uptake: OFF
-Fatty acid breakdown: ON to make glucose
-Ketogenesis: ON to make glucose
-Amino acid breakdown: ON to make Glucose
Which metabolic response is only present in T1D patients?
Ketogenesis: Last way to produce glucose
What is the overall response of the liver to low glucose in diabetes?
Type 1 patients make excess glucose via gluconeogenesis; break down fats to ketone bodies for glucose production;
-> appear to be “starving”.
