BM210 Block D Lecture 4

Hormonal Control of Metabolism

- To understand how metabolism changes in absorptive (fed) and post absorptive (fasted)
states.
- To explain how insulin is released in response to increase blood glucose.
- To describe how insulin and glucagon regulate metabolic pathways to control blood glucose.
- To demonstrate that loss of insulin and/or insulin resistance can cause diabetes

Glucose

- Key energy source

- Brain and nerves need glucose for energy
- Cant be sotred as high conc can disrupt osmotic balance of cell – would cause cell damage or
death
- Stored as a nonosmotically active polymer called glycogen

Glucose Homeostasis

- Blood sugar levels kept constatnt by range of homeostatic mechanisms

- When in excess glucose stored as glycogen or triglycerides
- When levels low these tissues become net exporters of glucose/fatty acids
- Hyperglycaemia – high blood glucose
- Hypoglycaemia – Low blood glucose

food intake regulated

- Brain integrate physiological info and external environment cues

- Brain play essential role in modulating appropriate reposnes to energy uptaken by body –
food
- Controlled by hypothalamus – when we are hungry and full
- Consume more energy than release = obesity
- Excess fat stored in adipocytes as triacyglycerols
- Hunger -send signals to from brain to gut to tell when hungry and need to eat,
- Satiety signals relayed from gut to brain to tell when full and reduce urge to eat

Control of Blood Glucose

- Controlled by complex mechanisms

- Various hormones released mainly from brain pancreas liver intestines and adipose tissue
- Insulin – released from pancreatic B cells when Glucose increase – decrease blood sugar
levels – stop it getting too high – signals fed state and remocal of glucose from blood
- Glucagon – released from pancreatic A cells when glucose decrease – increase blood sugar
level – stop it getting too low – signals release og glucose into blood

Absorptive (fed) and post-absorptive (fasted) states

- 2 distinctly different states in which the body must provide energy fro cellular activities
- Absorptive State
o Occurs after meal when body is digesting and absorbing nutrients
o Insulin involved in this- released from pancreatic b cells when after food intak e
o Allows fro energy storage
 o Regulated by insulin
o Glucose used by cells to produce energy atp
- Post absorptive state
o Occurs once food has been absorbed and digested and stored
o Glucose release to maintain blood glucose levels
o Stored energy is reserved fro use
o No nutrient absorption
o Fattu acids main energy source

Hormones

- Chemical messengers that are released from specific type of cell inreponse to specific signal
- Carried to target organ by circulatory system
- Long range effects – carrie din bloodstream
- Target cells express specific receptors that allow them to respond to hormone presence

Insulin Binding

- Binding of insulin to insulinreceptor (IR) leads to receptor auto-phosphorylation

- Phosphorylated residues on ir act as binding site for insuliln receptor susbtrate (URS)
- IR phosphorylate 4 tyrosine residues in IRS
- Lipid kinase bind to phosphorylated residues on irs and converts PIP2 to PIP3
- Bining of PIP3 activates PDK1 which then phosphorylates and activates kinases (PKB/AKT)

Akt/PKB activation

- Regulated by glycose uotak ein skeletal muscles, glycogen symthesis in liver and
gluconeogenesis in liver.
- Glucose transporter GLUT4 is insife the cell in GLUT4 storage vesivles (GSV)
- GSV stay inside cell and prevemt it from moving to plasma mem
- Activated PKB phosphorylate protein and inactivate it
- GLUT4 vesicles can then fuse with plamsa membrane – increase level of glucose transporter
at cell surface
- This is how insulin and pkb stimulate glucose uptake into muscle

Glycogen synthesis

- PKB activation leads to increase in glycogen synthesis

- Insuin signalling leads to PKB acgtivation
- PKB phosphorylates and inactivates GSK
- Leads to increasein active unohosphorykated form og glycogen synthease
- Increased activity of glycogen synthase increases glycogen synthesis

FOX01

- Insulin signalling lead to PKB activation

- PKB phosphorylates FOX01
- Prevents movement of FOX01 to nucleaus – loss of gluconeogenic gene expression and
glucose lose

Effects of PKA on metabolism

- Key effector of glucagn

 - Directly phosphorylates and inactivates glycogen synthase - block glycogen synthesis
- Activates glycogen phosphorylase leads to increased glycogen break down
- Activated key enxyame activity leasrs to increase glucose production

Leptin

- When fat storage hits certain level – leptin released from adipocytes
- Activation of leptin receptor in brain leads to changes in hunger sensation
- Obese have function ing leptin receptors and high blood conc of leptin – cant respond to
leptin effects – leptin resistance

Ghrelin

- Cells in GI Tract release ghrelin when stomach empty

- Acts on receptors n hypothalamus to increase hunger

Diabetes

- Defects in insulin release and action are associated with diabetes

- Type 1
o Arises due to insulin synthesis loss which is due to autoimmune destructin of beta
cells – cant be relaseasd
o Diagnosed in childhood
- Type 2
o Associated with insulin resisiatnce
o Decreased insulin secretion
o Generally occurs in adulthood