The Endocrine Pancreas - Part 1 Flashcards
What is body energy equal to?
Energy intake - energy output
What 2 hypothalamic centres determine energy intake by balance of activity?
Feeding centre - promotes feeling of hunger
Satiety centre - feeling of fullness by supressing feeding centre
What is the glucostatic theory?
Food intake is determined by blood glucose
As BG conc. increases then drive to eat decreases
What is lipostatic theory?
Food intake is determined by fat stores
As fat stores increase then drive to eat decreases
Leptin released by fat stores depresses feeding centres
What are the 3 categories of energy output?
Cellular work
Mechanical work - regulated voluntarily by skeletal muscle
Heat loss - counts for half of energy output
What are 3 elements of metabolism?
Extracting energy from nutrients in food
Storing that energy
Utilising that energy for work
What is the definition of metabolism?
Integration of all biochemical reactions in the body
What are anabolic and catabolic pathways?
Anabolic - build up, synthesis of large molecules from smaller for storage
Catabolic - break down, degradation of large molecules, releasing energy for work
What type of phase is the post absorptive phase?
Catabolic
What is an obligatory glucose utiliser?
Brain so BG conc. must be sufficient to supply brain even during fasted state
Failure causes hypoglycaemia
What is the normal range of BG levels?
4.2-6.3mM
Hypoglycaemia is under 3
What 2 endocrine hormones produced in pancreas maintain BG conc.?
Insulin and Glucagon
What is stimulated by insulin?
Lipogenesis
Glycogenesis
Metabolism in most tissues
What is stimulated by glucagon?
Glycogenolysis
Gluconeogenesis
Where are endocrine hormones released in pancreas?
Islets of Langerhans
What are the 4 types of islets cells?
Alpha
Beta
Delta
F cells
What do alpha islets cells produce?
Glucagon
What do beta islets cells produce?
Insulin
What do delta islets cells produce?
Somatostatin
What do F islets cells produce?
Pancreatic polypeptide
What happens if there is more insulin than glucagon?
Glucose taken up by cells from plasma lowering BG conc.
Increases glucose oxidation, glycogen synthesis, fat synthesis and protein synthesis
Describe insulin
Peptide hormone
Stimulates glucose uptake by cells
Only hormone which lower BG conc.
How is insulin synthesised and secreted?
Large preprohormone - pre-proinsulin which converted to proinsulin in the ER
Packaged as granules in secretory vesicles
Cleaved again to give insulin and C peptide
Stored till activated B cell
What stimulates release of insulin?
Mainly blood glucose conc.
Amino acids
How is glucose stored?
Mainly energy source in absorptive state
Excess stored as glycogen in liver and muscle
And as TAG in liver and adipose tissue
What is excess amino acids and fatty acids stored as?
Aa - converted to fat
FA - triglycerides in adipose tissue and liver
Describe the mechanism of control of insulin secretion by conc. of BG
Glucose is abundant so enters cells through GLUT and metabolism increases which increases ATP within cells
Katp channels to close - intracellular K conc. rises so depolarises cell
Voltage gated Ca channels open - trigger insulin vesicle exocytosis
Describe low BG conc. and insulin secretion
Katp channels are open so K flows out of cells causing hyperpolarisation
Voltage gated Ca channels remain closed and insulin not secreted
What is the primary action of insulin?
Binds to tyrosine kinase receptors on cell membrane of insulin dependant tissues to increase glucose uptake
In muscles and adipose tissue - stimulates specific GLUT4 which reside in cytoplasm
What happens when GLUT4 is stimulated in muscle and adipose tissue?
Migrates to membrane and is able to transport glucose
When stimulation by insulin stops then GLUT4 return to cytoplasm pool
What tissues are insulin dependant?
Muscles and fat
What GLUT transporters are not insulin dependant?
GLUT1 - basal glucose uptake in tissues
GLUT2 - similar
GLUT3 - b cells of pancreas and liver
Describe liver and glucose uptake
GLUT2 transporters and is insulin independent
Enters down conc. gradient
Glucose transport into hepatocytes is affected by insulin status
What happens in fed state in liver and glucose uptake?
Liver takes up glucose as insulin activates hexokinase which lowers glucose conc. in cells creating a gradient so movement in cells can happen
What happens in fasted state in liver and glucose transport?
Liver synthesises glucose via glycogenolysis and gluconeogenesis
Increases glucose conc. in cells so gradient favours glucose movement out of cell
What are some of the the additional actions of insulin?
Increase glycogen synthesis and inhibits glycogen phosphorylase
Promotes protein synthesis and inhibits proteolysis
Increases lipogenesis and inhibits lipolysis
Inhibits enzymes of gluconeogenesis
Permissive effect on GH
Promotes K ion entry stimulating NaKATPase
What happens when insulin binds to tyrosine kinase receptor?
Receptor phosphorylates insulin receptor substrates (IRS)
Second messenger pathways alter protein synthesis and existing proteins
Membrane transport or cell metabolism changed
What stimulates insulin release?
Increased BG conc.
Increased aa conc. in plasma
Glucagon
Other hormones controlling GI secretion
What stimuli inhibit insulin release?
Low BG conc.
Somatostatin
Sympathetic alpha-2 effects
Stress - hypoxia
Is IV or oral glucose has more insulin response?
Oral as increases insulin by direct effect in B cells and vagal stimulation of B cells plus incretin effects
