Type 2 diabetes

Question 1

Glucose- Insulin regulation in the fed state:

Answer 1

• High blood sugar, promotes insulin release from the pancreas
• In the fed states the liver will stop breaking down glycogen into glucose and instead store the glucose. This lowers the blood sugar.
• Insulin stimulates glucose uptake from blood into adipose tissues

Question 2

Glucose- Insulin regulation in the fasted state:

Answer 2

• Low blood sugar promotes glucagon to be released from the pancreas.
• Stimulates glycogen breakdown in the liver to make glucose and increase blood sugar

Question 3

How does our body maintain glucose homeostasis in the fed state:

Answer 3

• Balance glucose production by the liver during fasting
• Glycogenolysis: breakdown of glycogen for glucose, Glycogen is a storage form of glucose
• Gluconeogenesis: de novo glucose production. The body is making glucose from lipolysis and other substances from the body (glycerol and fatty acids). Reverse of glucose breakdown

Question 4

How does our body maintain glucose homeostasis in the fed state:

Answer 4

• Glycogenesis: makes glycogen from glucose in the liver
• Stops gluconeogenesis and lipolysis
  glycolysis: breakdown of glucose for energy

Question 5

Anatomy of the Pancreas:

Answer 5

• Alpha cell: produces the hormone glucagon, released in response to low levels of glucose
  -Beta cell: releases insulin, Step 1; glucose enters, step 2: atp to adp which changes the potassium channel. Step 3: voltage-gated calcium opens when from depolarization. The storage granules are then mobilized to the plasma membrane

Question 6

Insulin

Answer 6

• active hormone in pancreatic extracts that could lower glucose. Facilitates blood glucose uptake in skeletal muscle and adipose tissue

Question 7

How does insulin stimulate glucose uptake:

Answer 7

• Insulin (in the blood) binds to the receptor, it targets GluT4(cytosol)
• GluT4 mobilized to the plasma membrane and brings the glucose into the cell and metabolized or stored as glycogen or fats

Question 8

How is glucose transported into an adipocyte

Answer 8

• Insulin binds to receptors on target cell. This cause phosphorylation and mobilizaton of GluT4
• GluT4 translocates to the cellular membrane and binds glucose
• GluT4 and glucose are internalized and the glucose is released and metabolized into ATP, stored glycogen or fats

Question 9

Outcome of Insulin Signaling in an Adipocyte:

Answer 9

• Insulin stimulates glucose uptake
• Insulin stimulates lipogenesis
• Insulin blocks lipolysis

Question 10

Microvascular complications

Answer 10

• Eye: high blood pressure and high blood glucose damages the eye blood vessels
• Kidney: high blood pressure damages blood vessels and the excess blood glucose overworks the kidneys
• Neuropathy: hyperglycemia damages nerves in the nervous system. This results in pain and numbness

Question 11

Macrovascular complications

Answer 11

-Brain: Increased risk of stroke and cerebrovascular disease
- Heart: high blood pressure and insulin resistance increase risk of coronary heart disease
- Extremities: peripheral vascular diseases result from the narrowing of blood vessels increasing the risk for reduced of blood flow in the legs

Question 12

Type 1 vs Type 2 Diabetes:

Answer 12

• Type 1 (adolescents): The pancreas don’t produce insulin to stimulate glucose uptake
• Type 2 (adult): The pancreas has slight function and is able to stimulate glucose uptake however this becomes less and less. Cells fail to respond to insulin properly. Beta cells begin to die and not produce insulin and therefore will need insulin injections

Question 13

Type 1 Diabetes

Answer 13

• Antigen Presenting Cells (APCs) are exposed to insulin-producing cells in the pancreas
• These APCs travel to lymph nodes and other parts of the body that are involved in the immune system such as B cells and T cells against insulin-producing cells
• These B cells and T cells once activated, propagates this signal and proliferate(grow rapid)
• These cells then search out and destroy insulin-producing cells

Question 14

Type 2 Diabetes:

Answer 14

• Diet-induced or adult onset
• Impaired insulin action and release are accompanied by the inability of target tissues to take up glucose. A mixture of messed up insulin and adipose tissue to take up glucose
• Pancreatic beta cells begin to die and reduce their numbers to produce insulin

Question 15

Medical Progression of Type 2 diabetes:

Answer 15

• Overnutrition= increase in food consumption promotes excess fat accumulation in white adipose tissue
• Insulin resistance: chronic overnutrition leads to the inability of adipose tissue and skeletal muscle to take up glucose in an insulin-dependent manner. Results in elevated blood glucose. On the way type 2 diabetes
• Insulin Resistance: is reversible, exercises, and eats better. Type 2 diabetes is not. Characterized by high glucose levels. Does Not stimulate GluT4 when insulin binds to its receptor. OVERWORKED

Question 16

What happens when there’s a build up of glucose?

Answer 16

• The body thinks it’s in the fed state and the pancreas will continue to release more insulin to reduce the blood glucose. The pancreas becomes overworked and starts to die.
• The adipocyte is confused and thinks it’s in the FASTED STATE. Insulin stops glycolysis. Lipolysis increases because the body thinks there is no glucose present to be used as energy so instead it uses stored fats. Burning all of the lipids you have stored. De novo lipogenesis, TG synthesis, and Glucose uptake go down

Question 17

Evidence on Insulin Resistance:

Answer 17

• Lipid blocking of insulin receptor downstream signaling. The Lipids that are being exposed from enlarged adipocytes now in the free are blocking
• Adipocyte ER stress in Response to both inflammation and lipids

Question 18

Beta cell death:

Answer 18

• Being too overworked and starts making insulin mistakes that the cells begin to die and then it becomes Type 2 diabetes
• ER stress, if it can’t solve the misfolding problem
• Can’t be regenerated hence why type 2 diabetes is not reversible

Question 19

What initiates the whole process?

Answer 19

hyperinsulinemia cause insulin resistance and type 2 diabetes?

Question 20

Foxo1:

Answer 20

• transcription factor, regulates gene expression of hepatic gluconeogenic genes. Insulin suppresses its activity and has it degraded.

Question 21

If obesity-induced hyperinsulinemia cause insulin resistance and type 2 diabetes? TRUE

Answer 21

• This suggests chronic overnutrition forces the pancreas to overproduce insulin. But the adipocytes and muscle cells remain insulin sensitive unto the beta cell failure and the loss of insulin creates type 2 diabetes
• HFD stresses the beta cell which causes insulin secretion
• Chronic insulin leads to adipose inflammation but decreases in glut 4
• Adipose lipolysis increase
• Serum-free fatty acids increase insulin secretion and are independent of glucose

Question 21

If obesity-induced disruption of insulin signaling lead to hyperinsulinemia (high # of insulin the blood) and type 2 diabetes

Answer 21

• Hepatocyte (type of cell in the liver)
• Disruption in hepatic glucose production: foxo1 does not degrade but goes into the liver and makes it produce more glucose that’s released in the blood. Turns on genes to make glucose body thinks it’s in the fasted state and needs more glucose
• Increase foxo1

Question 22

lipogenesis:

Answer 22

excess glucose is synthesized into fatty acids

Question 23

Liver production occurs

Answer 23

because it believes the body is in the fasted state