Module 4 Flashcards
(19 cards)
1
Q
What is diabetes mellitus
A
high blood sugar resulting from defects in insulin secretion or action
2
Q
Symptoms of DM
A
- Polyuria
- Polydipsia
- Weight loss
- Blurred vision
3
Q
Type 1 DM
A
- due to pancreatic B-cell destruction
- prone to ketoacidosis
4
Q
Type 2 DM
A
resulting from the combination of insulin resistance with some defect in insulin secretion
5
Q
Components of diagnosis
A
- Glucose profile = glucose tolerance and fasting glucose
- insulin tolerance
6
Q
What additional things does diabetes cause
A
- retinopathy
- nephropathy
- amputations
- accelerates atheroscelorsis
7
Q
Glucose absorption and disposal
A
- After ingestion glucose is absorbed into the hepatic portal vein from the intestine
- 1/3 is taken up by the liver and the remaining 2/3 is delivered to other tissues via arterial blood
8
Q
Hepatic glucose uptake regulatory factors
A
- increase in the glucose load to the liver as a result of intestinal glucose absorption-induced hyperglycaemia
- negative arterial-PV glucose gradient generated by the absorption of glucose from the intestine into the PV making glucose levels higher
- hyperinsulinemia due to hyperglycemia induced secretion via islet B-cells
9
Q
Metabolic defects in diabetes
A
- increased hepatic glucose production
- decreased glucose uptake in skeletal muscles
- progressive insulin secretory
- impaired insulin signalling = deceased GLUT4 vesicle transport = decreased glucose uptake
10
Q
Exercise and glucose uptake relationship
A
- exercising mice with KO insulin receptors in skeletal muscle showed no development of diabetes but hyperlipidemia
- exercise activates a signalling pathway independent of the insulin receptor > increases AMPK stimulating GLUT4 translocation = glucose uptake
11
Q
KO insulin receptor in liver
A
KO in the liver of healthy mice developed glucose intolerance and insulin resistance = liver continues to pump glucose out as no insulin stop signal
12
Q
Adipokines
A
- protein factors secreted by adipocytes to regulate metabolism
- dysregulation leads to altered metabolism
13
Q
Insulin role
A
- inhibiting gluconeogenesis in the liver
- stimulating glucose uptake in muscles
- inhibiting lipolysis
14
Q
Insulin resistance
A
- initially B-cells will compensate by making more B-cells to produce more insulin but these will eventually fail so blood sugars increase = DM
- associated with the development of amyloid in the pancreas = kills B-cells
15
Q
Incretin response
A
- increased insulin secretion when glucose is ingested orally vs IV
- indicates something released from the gut in response to glucose which enhances glucose secretion
16
Q
GLP-1
A
- derived from post-translational processing of proglucagon in the intestine
- infusion lowers blood glucose in T2DM
- short half life as it is degraded rapidly by protease > FA attachment needed to allow for attachment of albumin to increase half-life
- delays gastric emptying = decreased rate of glucose entrance
- decreases appetite
- decreases glucose production
- enhances insulin secretion
- more effective in combination with GIP
17
Q
GIP
A
- Secreted by the duodenum
- has shared functions with GLP-1
- decreases bone resorption
- decreases appetite
- increases lipid accumulation
- increases insulin secretion
18
Q
Amylin
A
- pancreatic beta cell hormone that is co-secreted with insulin in response to nutrients
- limits the rate of gastric emptying
- reduces the secretion of glucagon
- works via direct brain activation
- observed loss of amylin secretion in T1DM rat models
- prone to aggregation so analogues need to be modified
- meal ending satiation is the major effect induced by amylin
- sensitizes models to leptin via IL-6 secretion= reduced food intake
- T2DM have elevated amylin in association with elevated insuin
- amylin is elevated in obese men
19
Q
Dual GLP-1 agonists and GIP antagonists
A
- blocks GIP receptor and stimulates GLP-1 receptor
- KO and LOF mutants in GIP receptors have been associated with a decrease in body weight and/or protection from weight gain in mice when fed a high fat diet
- have displayed a significant weight loss
