lecture 24 Flashcards
what does blood glucose homeostasis require?
effective regulation
(usually driven by insulin and glucagon)
what occurs to blood glucose after a meal?
-increase
-comes down with time
what occurs to insulin with low blood glucose levels?
insulin levels low
what occurs to insulin with high blood glucose levels?
insulin levels also high
what is hyperglycaemia?
blood glucose levels are too high
what does hyperglycaemia cause?
high blood glucose to stimulates insulin secretion
what occurs with hyperglycaemia and glucagon?
inhibits glucagon secretion
when is glucagon at highest?
when glucose levels are low
what is the role of insulin?
-secreted in conditions of high blood glucose
-insulin decreases blood glucose levels to normal range
what is the role of glucagon?
-secreted in conditions of low blood glucose
-increases the blood glucose levels
what occurs after a meal?
-increase blood glucose levels
-signals pancreas to release insulin
-insulin is signal to decrease blood glucose levels
where is the signal sent to?
liver, adipose tissue and muscle
what does the insulin signal mean?
increase glucose uptake, don’t produce any more glucose, form glycogen with the insulin
what occurs after exercise/prolonged periods of not eating?
-blood glucose decreases
-pancreas detects the change and releases glucagon
-glucose levels increased to normal range
where does the glucagon act upon?
liver
what are the main functions of the liver?
- exocrine - releases digestive enzymes into gut
- endocrine - blood glucose homeostasis
what are the pancreatic islets (islets of langerhans)?
-scattered throughout pancreas
-comprise of alpha, beta and delta that secrete hormones
-small and different
-regulate blood glucose
what do the pancreatic alpha cells release?
glucagon
what do the pancreatic beta cells release?
insulin
what do the pancreatic delta cells release?
somatostatin
what are the regulators of insulin release?
glucose
amino acids
gut hormones
neural input (cholinergic)
adrenaline (inhibitory action)
somatostatin (inhibitory action)
what are the regulators of glucagon release?
glucose (inhibitory action)
insulin (inhibitory action)
amino acids
neural input (stress)
adrenaline
cortisol
gut hormones (inhibitory action)
how is insulin produced by pancreatic beta cells? complex
-gene transcription produces unfolded structure
-needs to be folded so transported to ER
-forms preproinsulin (has n terminal signal peptide, beta chain of insulin connected to a chain)-not active
-cleaved to proinsulin
-transported to Golgi (packages proteins)- production off disulphide bonds between b and a chains
-cleavage of c peptide forming mature insulin
how is insulin formed? simple
-produced in islet beta cells as pre-proinsulin
-intramolecular disulphide bonds formed between b and a chains, cleaving a C-peptide (inactive) and insulin
how is insulin stored?
-hexatrimeric form (to add stability)
-complexed with zinc
what is C peptide used for?
-diagnosis (type 1 diabetes) to see whether people are producing their own insulin
-used as insulin has short half life
what occurs in basal/resting state?
-glucose moves via concentration gradient from blood into cell
-glucose needs to be metabolised in cell by glucokinase (low activity so not much glycolysis, low energy levels)
-potassium atp channels remain open
-voltage calcium channels closed at resting
-membrane hyperpolarisation
-no insulin secretion
what occurs with higher blood glucose levels?
-more glucose entering cell
-glucokinase activity higher so more metabolism
-raised ATP
-K+ channels closed
-membrane becomes depolarised
-Ca2+ channels open - influx into the cell
-high insulin secretion
what occurs in glucose metabolism?
-glucose is phosphorylated to G3P and metabolised by glycolysis and mitochondrial oxidation to generate ATP
what tissues does insulin affect in the postprandial state? (fed state)
-pancreas
-gut
-muscle
-adipose tissue
-brain
-liver
how is insulin used in the muscle?
-stimulation of insulin allows glucose into muscle
-insulin tells it to store glucose as glycogen or use for energy production
how is insulin used in the fat cells?
-insulin stimulates uptake of glucose
-stored as fat cells
what happens to the glucose taken up by the liver?
-converts to glycogen
-converts to fat (transported out to be taken up by adipose tissue)
what is glycogen?
why is glycogen needed?
-glucose brings water into cell and is osmotically active so cant store much in cell
-glycogen is major glucose store in muscle and liver
what is the aim of the glycogen store in the liver?
to maintain blood glucose levels when not eating
what happens when the liver glycogen stores are full?
-glucose is converted to fat by glycolysis
-enters citrate cycle forming fatty acids -eventually packaged into lipoproteins that are taken up by adipose tissue to be stored for later
what occurs in the liver in fasting state?
-glucose falling
-no insulin release from pancreas but glucagon release
-acts on liver as has receptors
-breaks down glycogen into glucose and release into bloodstream
-gluconeogenesis - converting other carbon precursors into glucose
-fatty acids made into ketone bodies which are taken into bloodstream - useful for brain as source of fuel
what occurs in the adipose tissue in a fasting state?
-in adipose tissue, triglyceride starts to break down back to fatty acids and are related into bloodstream (another energy source)
what occurs in the muscles in fasting state?
-muscle takes up fatty acids and uses for fuel
-muscle breaks down its protein to form amino acids
how is glucose produced during fasting?
- glycogenolysis (breakdown of glycogen)
- gluconeogenesis (making glucose from other carbon compounds)
what does insulin do in the muscle?
-increases glucose transport
-increase glycogen synthesis
-increase glucose oxidation
-increase protein synthesis
what does insulin do in the adipose tissue?
-increase glucose transport
-increase triacylglycerol synthesis
-decrease triacylglycerol breakdown release of fatty acids
what does insulin do in the liver?
-increase glycogen synthesis
-increase fatty acid and triglyceride synthesis
-increase protein synthesis
-decrease glycogen degradation
-decrease gluconeogenesis
what molecular targets are present in the muscle for insulin to have this effect?
-glucose isn’t taken up in absence of insulin because GLUT4 (glucose transporter) is localised to intracellular vesicles- needs insulin signalling for the translocation to plasma membrane
-insulin promotes the conversion to glycogen by activating glycogen synthase enzyme
-insulin covalently modifies the sensor (removes a phosphate group)
-stimulates glucose oxidation by phosphorylating pyruvate dehydrogenase so it becomes activated
what molecular targets are present in the adipose tissue for insulin to have this effect?
-increased translocation of GLUT4
-increased fatty acid synthesis by increasing acetyl-coA carboxylate and fatty acid synthase
-decreased hormone sensitive lipase by covalent modification
how does insulin regulate the fat uptake in adipose tissue?
-stimulate glucose uptake
-triglyceride synthesis
how is covalent modification activated in the liver?
glycogen synthase and acetyl coA carboxylase
how is covalent modification deactivated in the liver?
phosphorylase
how is gene transcription induced?
glucokinase, acetyl coA carboxylase, fatty acid synthase
how is gene transcription repressed?
glucose 6 phosphatase
