Type I Diabetes Flashcards
(38 cards)
Pancreas
glandular organ in the digestive and endocrine systems of vertebrates
functions as an exocrine and endocrine gland
drains directly into duodenum
highly vascularised
Exocrine gland
secretes enzymes that aid digestion and absorption of nutrients
Endocrine gland
synthesises important metabolic hormones such as insulin, glucagon and somatostatin
Pancreatic exocrine secretions
Enzymes digest proteins, carbohydrates and lipids; high bicarbonate concentration neutralises stomach acid
Secretion controlled by hormones released in stomach (i.e. gastrin)
Exocrine secretions released into pancreatic duct by two main cell types
Proteases such as trypsinogen and chymotrypsinogen, plus pancreatic lipase and amylase
Released as zymogens (proenzymes) to prevent autodigestion before reaching site of action; activated in gut by enteropeptidase (and then trypsin) → broken down so they can function as enzymes
Ductal cells
release bicarbonate
Acinar cells
synthesise and release enzymes
Islets of Langerhans
Clusters of endocrine cells - up to 1 million clusters, closely associated with local capillary network within the pancreas
contain multiple cell types
Main role of endocrine secretions
regulation of glucose metabolism and blood glucose concentration
Alpha (α) cells
release glucagon (increases blood glucose)
Beta (β) cells
release insulin (decreases blood glucose)
Delta (δ)cells
release somatostatin (inhibits a and β cells function)
Gamma (γ) cells (PP cells)
release pancreatic polypeptide
Importance of glucose regulation
- Glucose is key energy source for mammalian cells; CNS in particular
- Need adequate supply to cope with variable demands & intermittent food intake - so we don’t have to eat all the time
- Feeding provides more energy than immediately required; excess stored as glycogen (in liver) or fat (in adipose tissue)
- Energy stores are mobilised between meals and during fasting
Insulin
the main regulatory hormone, encourages cellular uptake of glucose and utilisation or storage of energy derived from glucose
Actions of insulin
- Actions on liver, fat and muscle
- Encourages conservation of energy
- Regulates glucose utilisation
Regulation of insulin secretion (β cell)
Glucose transport through GLUT1/2 receptor
Glucokinase - phosphorylates glucose to undergo glycolysis
ATP - from krebs cycle
Kir6.2 channel - ATP blocks this potassium-gated ion channel, causing depolarisation of membrane
L-type Ca2+ channel - influx of calcium
Increase in [Ca2+]i - intracellular calcium, stimulates pool of insulin
Release of insulin - immediately releasable pool of insulin
Reserves of insulin - reserve pool primed when immediately releasable pool is depleted
biphasic release of insulin
Insulin - structure
- Peptide hormone
- Two chains of amino acids (21aa & 30aa)
- Linked by disulphide bridges
- First protein ever to be sequenced
- Frederick Sanger (Cambridge, 1952)
Cellular effects of insulin
-insulin acts on other cells locally, binding to insulin receptor stimulating MAP kinase signalling pathway and PI-3K signalling pathway
-PI-3K stimulates GLUT4 production, facilitating its trafficking in vesicles to cell membrane → able to take in more glucose and store it
-fat, liver and muscle tissue
MAPK signalling pathway
cell growth, proliferation, gene expression
PI-3K signalling pathway
synthesis of lipids, proteins and glycogen
cell survival and proliferation
GLUT4 production and trafficking to membrane - facilitates glucose uptake
Insulin inhibits (metabolic)
gluconeogenesis
glucogenolysis
lipolysis
ketogenesis
proteolysis
Insulin promotes (metabolic)
glucose uptake in muscle and adipose tissue
glycolysis
glycogen synthesis
protein synthesis
uptake of ions (especially K+ and PO4-3)
Diabetes mellitus
Excess blood glucose (hyperglycaemia) is characteristic symptom → inability to control blood glucose
Fasting plasma glucose > 7 mmols/L
Post-prandial glucose > 11 mmols/L
Glycated HbA1c > 7 %
Acute clinical signs of diabetes
Glycosuria - sugar in urine
Polyuria - increased urine production
Polydipsia - excessive thirst
multiple metabolic and physiological consequences