Lecture 35 - Fuel Mobilisation #1 Coordinating Metabolism Diabetes (Type II)

Distinguish between type I and type II diabetes.

Type 1 Diabetes usually occurs during early childhood and its when the body does not produce sufficient insulin and is caused by destrucution of beta cells and requires insulin injections to regulate the glucose levels.


Type 2 Diabetes occurs in adulthood and is when the body does not respond to insulin and is caused by down regulation of insulin receptors. it can be controlled with a carefully monitored diet.

What are some symptoms' related to type II diabetes.

urinating more often than usual, particularly at night.

feeling very thirsty.

feeling very tired.

unexplained weight loss.

What is Glycated haemoglobin (HbA1c)?

When glucose builds up in your blood, it binds to the haemoglobin in RBCs. The HbA1c test measures how much glucose is bound. As RBCs live for about 3 months, the test shows the average level of blood glucose for the past 3 months.

Explain why glycated haemoglobin is used for diabetes diagnosis.

bA1c reflects average plasma glucose over the previous eight to 12 weeks (15). It can be performed at any time of the day and does not require any special preparation such as fasting.

What is the concepts of insulin resistance (IR)?

Reduced response to the same amount of insulin.

Decreased glucose uptake and increased gluconeogenesis are prominent features as is elevated blood FFAs.

The hyperglycaemia induced by IR causes the pancreas to produce more insulin but eventually the beta-cells response diminishes, and insulin levels drop

What happens in the IR?

There is evidence of reduced levels of phosphorylation and mis phosphorylations in insulin signalling proteins which reduces GLUT4 translocation likely promoted by FFAs, inflammatory cytokines and oxidative stress

What are some treatments that can be used for treating type II?

lifestyle changes

drugs

Treatments are mainly aimed at promoting insulin secretion and improving insulin sensitivity.

Insulin use

What is Metformin?

It is used to treat type 2 diabetes.

Both metformin and exercise increase AMP levels, which will activate AMPK, which will reduce gluconeogenesis. This will reduce blood glucose levels.

What is GLP-1 Agonists?

It is used to treat type 2 diabetes.

GLP-1 potentiates insulin secretion in b-cells

Peptide hormone synthesised in the intestine.

Synthesised in response to nutrients

Made from glucagon via convertase enzyme.

Acts through its receptor to stimulate insulin secretion.

What is SGLT2 inhibitors

It is used to treat type 2 diabetes.

The SGLT1 sodium/glucose transporter absorbs glucose in the intestine.

SGLT2 is a similar transporter expressed in the kidney proximal tubule where it reabsorbs glucose back into circulation.

Inhibiting it allows glucose to remain in urine for excretion and hence lowers blood glucose levels

Describe what a glucose tolerance test is and contrast results for a normal, diabetic and prediabetic person.

A glucose tolerance test (GTT) measures how efficiently the body processes glucose. The person fasts overnight, consumes a glucose solution, and blood glucose levels are measured at intervals (typically 2 hours).

A normal person blood glucose will rise after consuming the glucose solution but will then return to normal quickly

Prediabetic persons blood glucose is higher than normal but not yet in the diabetic range

Diabetic person blood glucose remains elevated above the diagnostic threshold

Describe what glycated haemoglobin is and why it is used to diagnose diabetes.

The HbA1c test measures how much glucose is bound. As RBCs live for about 3 months, the test shows the average level of blood glucose for the past 3 months

Describe two biochemical features of insulin resistance.

Impaired insulin signaling: In insulin-resistant states, signaling pathways that mediate glucose uptake (like the PI3K/AKT pathway) are downregulated, leading to reduced glucose absorption by muscle and fat cells.

Increased hepatic glucose production: Insulin normally inhibits the liver's production of glucose, but in insulin resistance, this inhibition is reduced, leading to higher glucose output by the liver

Name a drug that enhances insulin sensitivity and describe how it works.

Metformin is a drug that enhances insulin sensitivity. It works by decreasing hepatic glucose production and increasing glucose uptake by muscles. It activates AMPK, which improves insulin sensitivity and reduces liver glucose production, helping lower blood glucose levels in people with Type II diabetes.