25 Regulation of blood glucose levels by pancreas Flashcards
what happens in the absorptive state
ingested nutrients enter blood from GI and support energy requirements of body
excess nutrients are STORED to use in post absorptive state
what happens in post absorptive state
no nutrients are entering blood from GI
net catabolism of stores happens
post absorptive state must maintain blood glucose levels in absence of absorption
how do cells make ATP
using carbon sources - glucose etc
what is glucose mainly used fro in absorptive state
- used for energy
- storage as glycogen in liver and skeletal
- storage as fat in adipose
what is the only organ that can produce glucose in PA state
the liver
how does liver produce glucose
via gluconeogenesis and glycogen breakdown
what is essential for regulation of blood glucose
insulin – as glucose increases so does insulin
what do pancreatic islets do
contain cells that secrete insulin and glucagon
what cells do islets have
alpha and beta cells
what do alpha and beta cells secrete
alpha produce glucagon
beta produces insulin
are glucose and insulin peptide or steroid hormones
peptide
what does increase stimulate in liver, skeletal muscle and adipose
- increased glucose uptake
- increased glycolysis
- increased glycogen synthesis (liver and skeletal)
what does insulin inhibit in liver
- inhibit gluconeogenesis
- inhibit glycogen breakdown
what does insulin inhibit in skeletal muscle
glycogen breakdown
how does glucose regulate insulin release from beta cells
- increased uptake and metabolism of glucose leads to increase in ATP:ADP ratio
- increased ATP:ADP leads to CLOSURE of ATP-sensitive K+ channels and membrane depolarisation
- depolarisation of membrane leads to opening of voltage gated Ca2+ channels
- regulating increase in cytosolic Ca2+ promotes secretion of insulin via exocytosis of insulin granules
what happens when ATP binds to ATP-sensitive K+ channels
it closes the channel and leads to higher K+ in the cell
activation of protein kinase B steps
- insulin binds to insulin receptor (IR) and leads to auto receptor phosphorylation
- phosphorylated residues on IR act as binding sites for IR substate (IRS) proteins
- IR phosphorylates IRS proteins
- phosphoinositide 3-kinase binds to phosphorylated residue on IRS proteins and the converts the membrane lipid PIP2 into PIP3
- binding to PIP3 activates PDK1 which phosphorylates and activates PKB
- activated PKB mediates many of the intracellular effects of insulin
what is a key output of insulin binding
activation of protein kinase
what do kinases do
add phosphate to proteins
what are insulins important targets
liver, skeletal muscle and adipose tissue
how does insulin stimulate glucose uptake into skeletal muscle and adipocytes
by increased amounts of GLUT4 at the cell surface
what is a key step in regulating insulin stimulated GLUT4 vesicle exocytosis
protein kinase B activation
is anything soluble at the surface released during exocytosis
yes
what is the activity of glycogen synthase regulated by
phosphorylation
glycogen synthase is phosphorylated by GSK and made inactive
what does PKB activation lead to
an increase in glycogen synthesis
how does PKB activation cause increase in glycogen synthesis
- insulin signalling leads to activation of PKB
- PKB phosphorylates and inactivates GSK
- this leads to an increase in the active form of glycogen synthase (non-phosphorylated)
- increased activity of glycogen synthase increases glycogen synthesis
what is gluconeogenesis regulated by
the transcription factor Fox01
how does Fox01 work
its a transcription factor that regulates expression of gluconeogenic genes
Fox01 is synthesised in the cytosol but moves to the nucleus to perform this function
how does insulin inhibit gluconeogenesis in liver
by affecting transcription of gluconeogenic genes
does PKB activation by insulin lead to a decrease in gluconeogenesis
yes by phosphorylating Fox01 which prevents it from entering the nucleus
this turns off expression of gluconeogenic genes
what causes type 1 diabetes
a loss of insulin synthesis/release from pancreatic beta cells
(autoimmune destruction of beta cells)
what causes type 2 diabetes
insulin resistance of target tissues and decreased insulin secretion
(contribution of these factors differs between individuals)
how to treat type 1 diabetes
diet and lifestyle, insulin
type 2 diabetes treatment
- diet and lifestyle
- metformin (suppresses glyconeogenesis)
- sulfonylureas (increase insulin release from pancreatic B cells)
- insulin
what causes metabolic changes in the PA state
a consequence of the lack of insulin
what does glucagon do
increase blood glucose levels
what is the only organ that can release significant amounts of glucose into the blood
the liver as it expresses glucose-6-phosphase
why do A cells in islets secrete glucagon
to maintain blood glucose levels and prevent hypoglycaemia
what plays the most important role in metabolic changes in the PA state
insulin, although glucagon plays a significant role
what does binding of glucagon to its receptor do
lead to an elevation in cAMP levels and activation of PKA
what is glucagons main target
the liver
how does glucagon stimulate glycogen breakdown
- PKA phosphorylates PK (phosphorylation kinase) increasing its activity
- PKA phosphorylates glycogen synthase, decreasing its activity
what is released when fat storage hits a certain level
leptin is released from adipocytes – activation of leptin receptors in hypothalamus leads to changes in sensation of hunger
