Endocrine 2 - Endocrine Pancreas

Question 1

What does the endocrine portion of the pancreas do?

Answer 1

It controls glucose, lipid and carbohydrate metabolism in the whole body

Question 2

What are the 4 main cell types found in the endocrine pancreas?
What hormone does each cell type secrete?

Answer 2

Alpha cells (15-20%) - Glucagon: negative regulation of insulin
Beta cells (60-70%) - Insulin: negative regulation of glucagon
Gamma cells (5-10%) - Somatostatin: reduces stomach acid secretion, negative regulation of insulin, glucagon + PP, suppresses exocrine function through CCK
PP cells cells (1-2%) - Pancreatic Polypeptide: stimulates gastric juice secretion, regulates endocrine + exocrine function of pancreas, secreted when BSLs are low

Question 3

What are 2 conditions T1DM patients can develop if they do not receive insulin when required?

Answer 3

1. Ketoacidosis

2. Coma

Question 4

What happens in KETOACIDOSIS?

Answer 4

• Decrease in insulin and therefore your body perceives a relative increase in glucagon
• This lack of insulin means body can’t take up as much glucose and therefore we need to find alternate energy stores
• Glucagon stimulates gluconeogenesis –> INCREASE IN BGLs
• Excessive ketones (fat breakdown) –> decrease in blood pKa (metabolic acidosis)
• Kidneys filter excess glucose (and with this water also follows the glucose) –> polyuria + polydypsia + dehydration

Question 5

GENETICS and T1DM

T1DM is associated with 2 other AUTOIMMUNE diseases. What are they?

Answer 5

1. Thyroid - Hashimoto’s
2. Small intestine - coeliac disease
   * ** However, unlike other autoimmune disorders, some halotypes can be protective against T1DM
   * ** If a patient has either (1) or (2) they will be tested for T1DM.

Question 6

What 3 tests are used to diagnose DM?

Answer 6

1. Random glucose test >200mg/dL
2. Fasting > 126 mg/dL more than one occasion
3. abnormal OGTT >200mg/dL after 2 hours

Question 7

Type 1 DM is characterised by ______ insulin deficiency.

Type 2 DM is characterised by beta cell ______ + ______ insulin deficiency.

Answer 7

T1DM: absolute
T2DM: exhaustion, relative

Question 8

Genome-wide association studies have identified

multiple genetic susceptibility loci for T1DM. What are 3 of particular interest?

Answer 8

IDDM1, IDDM2, IDDM12

Question 9

_____ area on the genome contains ______ found on Chromosome __ which encodes for _______.

HLA contains many different halotypes. 90-95% of Caucasion people with T1DM exhibit the halotype HLA-DR_ or _______.

Heterozygous HLA-DR3 and HLA-DR4 is thought to be the _____ risk of developing T1DM.

Which halotype of HLA is though to be protective?

Answer 9

IDDM1, Human Leukocyte Antigen, 6, Major Histocompatibility Complex.

HLA-DR3 or HLA-DR4

Highest

HLA-DR2 - though to be protective

Question 10

IDDM2 and IDDM12 are non-HLA genes but still are thought to be a genetic cause of T1DM.
IDDM2 is found on Chromosome __ and codes for _____. Within this there are VNTR - Class I ___ the risk of T1DM and Class III ____ risk of T1DM.
IDDM12 is found on Chromosome __ and codes for _____.

Answer 10

11, Ins (insulin)
2, CTLA4

Increases, decreases

Question 11

What 4 ENVIRONMENTAL factors could be responsible for actioning the latent “pre-diabetic” period into an immune response causing beta-cell destruction

Answer 11

1. Viruses e.g. mumps
2. Environmental toxins
3. Foods e.g. gluten, cow milk protein
4. Gut microbiome

Question 12

What are the 3 proposed mechanisms for the way environmental factors cause T1DM?

Answer 12

1. Bystander Damage: infections cause islet damage and inflammation, resulting in release of beta-cell antigens and autoreactive T-cells
2. Molecular Mimicry: viruses produce proteins that mimic beta-call antigens. The immune reaction to these proteins cross-reacts with self-tissue (cos they are so similar)
3. Viral Deja Vu: viruses obtained during childhood persist (predisposing virus), or very similar ones (precipitating virus) develop, resulting in an immune response

Question 13

What is the ‘hygiene hypothesis’?

Answer 13

Some infections may be protective - the more frequently you are exposed to pathogen then the more your body expects it and the more in tune your immune response is.

Question 14

________ T-cells directly kill beta-cells.
________ T-cells injure beta-cells.
These cells are released during _____.

Answer 14

CD8+ Cytotoxic
CD4+ Helper
INSULITIS

Question 15

____ HbA1c has been associated with a _____ in diabetic complications.

Answer 15

Decreased, decrease

Question 16

What is the main goal of diabetes management?

Answer 16

Maintenance of a euglycaemic state