L7 pancreas Flashcards
anatomy and location
behind stomach, 15cm long, lobulated (lobes)
head+body+tail, where the head is tucked into inner curvature of duodenum. the body is the longest part and the tail ends adjacent to the spleen
main pancreatic duct and accessory duct run throughout the body, the main duct joins with the common bile duct, forming the hepatopancreatic ampulla
microscopic anatomy
contains islet of Langerhans, alpha (produce glucagon) and beta (produce insulin), pancreatic acinar cells, and duct
acinar and duct cells secretions
acinar secretes digestive enzymes, and duct secretes bicarbonates
pancreatic juice contains these secretions
hormonal control of pancreas
by secretin and CCK. CCK causes release of digestive enzymes from acinar cells. secretin causes bicarbonate release
pancreatic juice composition
1.4L produced per day
bicarbonate
- neutralises acidic chyme
- pH ~8
- amount of stomach acid produced is balanced by chyme
pancreatic proteases
- released as zymogens (eg trypsinogen)
- activated in duodenum (eg trypsinogen –> trypsin)
amylase, lipase, nucleases (all secreted in active form but require ions or biles to work)
function of islets of langerhans
- endocrine
- alpha and beta cells secrete glucagon and insulin respectively
- delta cells secrete somatostatin
- PP cells secrete pancreatic polypeptide (regulate gastric secretion)
- regulates transition between absorptive and post-absorptive stages
function of pancreatic ducts
- exocrine
- releases digestive enzyme (protease, peptidase, amylase, lipase, nuclease)
- secrete bicarbonate ions
glucose metabolism
GLYCOGEN –glycogenolysis–> GLUCOSE –glycolysis–> PYRUVATE
PYRUVATE –gluconeogenesis–> GLUCOSE –glycogenesis–> GLYCOGEN
insulin effect on skeletal muscle, liver, adipose tissue
- on skeletal muscle: increase take up of glucose from blood and increase uptake of amino acids
- on liver: increase take up of glucose and decrease breakdown on glycogen to glucose
- on adipose tissue: increase take up of glucose
insulin
small peptide hormone prod by beta cells
glucagon
small polypeptide hormone prod by alpha
glucagon effect on liver
- increase breakdown of glycogen
- increase uptake of amino acid and glycerol
- decrease conversion of glucose to glycogen
why is glucagon released in times of starvation, exercise and stress
to mobilise glycogen when glucose is needed by the muscles or when glucose is in short supply.
roles of parasympathetic NS
innervates islet of langerhans
- ACh stimulates insulin release during ingestion
roles of sympathetic NS
innervates islet of langerhans
- noradrenaline increases glucagon release and inhibits insulin release
glucocorticoids in glucose regulation
from adrenal cortex, released in times of physical and eternal stress.
- increases gluconeogenesis
- decreases glucose utilization by cells
- increase fatty acid release from adipose tissue
somatostatin in glucose regulation
from delta cells, decrease release of insulin and glucagon
glucose sensor
islets of langerhans contain GLUT-2 (glucose transporter 2) which are responsible for facilitating the entry of glucose into the beta cells.
glucose stimulated insulin release from beta cells
1) glucose uptake and phosphorylated by glucokinase
2) glucose metabolism generates pyruvate, which is then taken up by mitochondria, that is used for the production of messengers involved in exocytosis
3) glucose metabolism also triggers the production of cAMP, and increases the intracellular ATP, thus inhibiting the KATP (potassium ATP gated channels) so membrane becomes depolarized. this activates the voltage gated Ca channels to open, thus there is an influx of calcium.
4) increased Ca levels stimulate the exocytosis of insulin vesicles. the production of cAMP amplifies the glucose signaling pathways, enhancing insulin release.
pancreatic hormone receptors
glucagon receptor: GPCR (G protein coupled receptor), primarily in liver cells
insulin receptor: RTK (tyrosine kinase receptor)
signaling pathway of the glucagon receptor
- glucagon binds to the glucagon receptor on the cell surface
- the receptor activates G-proteins, particularly Gs proteins.
- Gs proteins activate adenylate cyclase.
- adenylate cyclase produces cAMP as a second messenger.
- cAMP activates protein kinase A (PKA).
- activated PKA phosphorylates target proteins.
- phosphorylation events regulate glycogenolysis, gluconeogenesis, lipid metabolism, and gene expression.
- cellular responses include increased glucose release, enhanced glucose production, lipid breakdown, and gene expression changes.
insulin receptor signaling pathway
- insulin binds to the insulin receptor on the cell surface.
- binding activates the insulin receptor, causing autophosphorylation of tyrosine residues on the receptor.
- phosphorylated tyrosine residues serve as docking sites for signaling proteins, such as insulin receptor substrates (IRS).
- IRS proteins are recruited and phosphorylated by the insulin receptor.
- phosphorylated IRS proteins activate downstream signaling pathways, including the phosphoinositide 3-kinase (PI3K) pathway and the mitogen-activated protein kinase (MAPK) pathway.
- the PI3K pathway promotes glucose uptake, glycogen synthesis, and protein synthesis.
- the MAPK pathway regulates cell growth, differentiation, and gene expression.
- activation of these pathways leads to the cellular responses of increased glucose uptake, enhanced glycogen storage, protein synthesis, and cellular growth and differentiation.
diabetes mellitus
affects 2% of the western population, caused by an insulin deficiency or complete lack of insulin or a lowered response of cells to insulin
T1DM
insulin dependent
affects 15% of diabetics
cause: destruction of beta cells (eg autoimmune)
treatment: insulin administered by injection
T2DM
non-insulin dependent
cells are insulin resistant even though insulin levels normal
cause: disruption to insulin receptor or signaling pathway, associated with obesity
treatment: diet control and exercise
GDM
gestational diabetes
in pregnant women with no prior diabetes
may be caused by natural interference with insulin receptors
usually recovers after delivery
4% of preg women
persistent hyperglycemia increases risk of intrauterine fetal death (still birth, dies in womb) to big baby (macrosomia)
diabetes insipidus
excessive thirst, lots of very dilute urine
causes:
- central (neurogenic): lack of vasopressin (ADH)
- nephrogenic: kidney does not respond
- dipsogenic: damage of thirst mechanism in hypothalamus
hyperinsulinism
NS deprived of glucose – anxious, nervous, sweat, tremble, coma
cause: benign tumor of islets of langerhans, uncontrollable insulin production
treatment: administration of lots of glucose and administer glucagon
pancreatitis
usually caused by alcohol (chronic pancreatitis) or gallstones (acute), but can be caused by high triglyceride levels (>1000mg/dL)
pancreatic cancer
1) exocrine
- adenocarcinoma (85%) or
- arises from pancreatic duct epithelium
- starts in the head
- acinar cell carcinoma (5%)
- increased prod of enzmes
2) neuroendocrine
- pancreatic neuroendocrine tumors (PaNETs) can be benign or malignant
- can be functioning or non functioning (producing hormones)
