L13: The endocrine pancreas Flashcards
Where is the pancreas located?
Upper left region--> Left hypochondriac Upper middle region--> Epigastric region Posterior to the stomach Head nestled in curvature of duodenum Tail towards the spleen
Which part of the gut does the pancreas develop from? Therefore, what is its blood supply?
Foregut
Coeliac blood supply
What are the functions of the pancreas?
Exocrine–> secrete digestive enzymes into the duodenum (majority of gland)
Endocrine–> secrete hormones into the blood stream , from Islets of Langerhans
What is different in structure between the endocrine and exocrine portion of the pancreas?
Endocrine–> cells cluster–> good blood supply
Exocrine–> cells form acinir–> around a duct
What are the important hormones secreted by the pancreas? Which cells produce them?
Polypeptide hormones Insulin --> β cells Glucagon--> α cells Somatostatin--> δ (delta) cells Pancreatic Polypeptide --> PP cells Ghrelin--> E cells Gastrin--> G cells Vasoactive Intestinal Peptide--> VIP cells
What two hormones are the most important for regulation of plasma glucose?
Insulin –> lowers plasma glucose
Glucagon–> Increases plasma glucose
Regulation of metabolism of carbohydrate, proteins and fats
Compare the actions of insulin and glucagon?
Insulin --> Feeding --> Liver, adipose tissue, skeletal muscle --> carbohydrate, proteins and lipids --> Anabolic Glucagon --> Fasting --> Liver, adipose tissue --> Carbohydrate and lipids --> Catabolic
Why is plasma glucose tightly controlled?
Brain uses glucose at fastest rate
Blood–> sensitive to changes in glucose, increase or decrease in osmolarity, circulation of glucose controlled
What the normal level for blood glucose?
Normal= 3.3-6 mmol/L
After meal 7-8 mmol/L
Renal threshold- 10mmol/L
What is meant by renal threshold? When is it normal to be above or below?
Level at which the kidney can no longer deal with plasma glucose
>10 mmol/L –> glucosuria (glucose in urine)
Pregnancy renal threshold decreases
Elderly renal threshold increases
What are the properties of insulin and glucagon?
Water soluble hormones
Dissolve in plasma–> no transport proteins required
Short T1/2–> 5 mins –> responsive to changes in eating habits, not hanging around
Interact with cell surface receptors
Inactivated by internalisation–> destroyed
What is the function of insulin?
Carbohydrate metabolism --> ↑ Glucose transport into cells --> ↑ glycolysis, by ↑ hexokinase and 6-phosphofructokinase activity --> ↑ glycogen synthesis, ↓ breakdown Lipid metabolism --> ↓ lipolysis --> ↑ FA synthesis and TAG synthesis --> ↑ uptake of TAG from blood --> ↓ FA oxidation in muscle and liver Proteins metabolism --> ↑ transport of AA into tissues --> ↑ proteins synthesis in muscle, adipose tissue, liver and other tissues --> ↓ protein degradation in muscles Anabolic Anti-gluconeogenic Anto-lipolitic and anti-ketotonic
How is insulin synthesised?
- Pre-proinsulin synthesis on rER -> single 109 aa
- Once entered the cisternal space, signalling peptide is removed (23aa) –> Proinsulin
- Proinsulin folds –> disulphide bonds form between cysteine residues
- Proinsulin–> rER to golgi where it is packaged for secretion
- Proteolysis in secretory vesicle removes connecting peptide C-peptide from middle of chain
- Mature insulin–> two chains held together by disulphide bonds
- Marginated to cell surface in pancreatic β cell until stimulated for release–> exocytosis
What is the structure of insulin? How does this compare to proinsulin and pre-proinsulin?
Big peptide–> 51 aa–> alpha helix structure
Two unbranched peptide chains held together by disulphide bonds
Proinsulin–>2 polypeptide chains, A and B chains, with C-peptide connecting them and disulphide bonds between cysteine residues
Pre-proinsulin–> signal sequence attached
What is contained within the secretory vesicle?
Insulin and C peptide
Stored as crystallin zinc-insulin compound
