Lecture 7.2: Control of Appetite Flashcards
What is a C-Peptide Test?
A C-peptide test is a blood test which is carried out to find out how much insulin your body is producing
Why is a C-Peptide Test useful?
It may be useful for determining whether a patient has type 1 or type 2 diabetes or whether they have insulin resistance
What is C-Peptide?
• C-Peptide is released at the same time as insulin
• For each molecule of insulin produced there is a molecule of C-Peptide
• C-Peptide does not itself influence blood sugar
• C-Peptide is a useful marker of insulin production because C-Peptide
tends to remain in the blood longer than insulin
What does C-Peptide do?
It helps with the correct folding of insulin and in the formation of disulphide bonds
Energy Balance: Intake and Expenditure
Intake: Carbohydrates, Lipids, Proteins
Expenditure: BMR, Physical Activity, Diet Induced Thermogenesis
Energy Imbalance
Energy intake > Energy expenditure –> ↑ energy stores and body weight
Energy intake < Energy expenditure –> ↓energy stores and body weight
Where is the appetite control centre?
Appetite Control Centre aka Satiety Centre
Located in the arcuate nucleus within the hypothalamus
Other brain areas are also involved in controlling appetite
What Two Types of Neurones does the Arcuate Nucleus Contain?
Primary Neurones: sense metabolites in blood and respond to hormones
Secondary Neurones: receive input from primary neurones, co-ordinate a response
Neurones of the Arcuate Nucleus
Two types of primary neurones:
Stimulatory (orexigenic) neurons: releasing Neuropeptide Y (NPY) and Agouti-related peptide (AgRP), promote hunger
Inhibitory (anorexigenic) neurons: releasing pro- opiomelanocortin (POMC) and cocaine and amphetamine-related transcript (CART), promote satiety
Central Pathways in the Arcuate Nucleus
These central pathways are influenced by peripheral signals which stimulate or inhibit appetite (majority of them are inhibitory)
The central pathways interact with each other and feed into lateral hypothalamus
Lateral hypothalamus communicates with other parts of brain and influences the ANS and feeding behaviour
Peripheral Signals: Appetite Stimulating
Ghrelin (stomach)
Peripheral Signals: Appetite Suppressing (Pancreas) (3)
• Insulin (pancreas)
• Amylin (pancreas)
• Pancreatic polypeptide and enterostatin (pancreas)
Peripheral Signals: Appetite Suppressing (Adipose Tissue)
• Leptin (adipose tissue)
Peripheral Signals: Appetite Suppressing (Intestines) (4)
• Cholecystokinin (CCK) (duodenum and jejunum)
• Glucagon-like peptide (GLP-1) (ileum and colon)
• Peptide YY = peptide tyrosine tyrosine (PYY) (ileum and colon)
• Oxyntomodulin (colon)
Signals From the Body to the Hypothalamus: Leptin
Polypeptide (145 aa) hormone released into blood from adipocytes
Stimulates the inhibitory primary neurones and inhibits the stimulatory primary neurones
Leptin induces expression of UCP in mitochondria leading to energy dissipation as heat
Overall effect is suppression of appetite, used clinically to treat obese patients lacking the hormone
Signals From the Body to the Hypothalamus: Insulin
• Polypeptide (55 aa) hormone released to blood from β-cells
• Suppresses appetite by similar mechanism as leptin
• Seems to be less important than leptin in feeding
Signals From the Body to the Hypothalamus: Amylin
Polypeptide (37 aa) hormone secreted by β-cells in pancreas
Roles not fully understood but known to suppress appetite, decrease glucagon secretion and slow gastric emptying
Pramlintide is an amylin analogue approved for treatment of Type 2 diabetes
Signals from the Gut to the Hypothalamus: Ghrelin
Peptide (28 aa) hormone released from stomach wall when empty
Stimulates the stimulatory primary neurones in arcuate nucleus to promote appetite
Filling of stomach (distension) inhibits ghrelin release
Signals from the Gut to the Hypothalamus: PYY/Peptide YY
Peptide (36 aa) hormone released from the ileum and colon in response to feeding
Inhibits the stimulatory primary neurones and stimulates the inhibitory neurones to suppress appetite
Orexigenic Neurones: What are they? What hormones affect them? What neurotransmitters/receptors are involved?
Orexigenic neurones stimulate eating and are neuropeptide hormones
PYY (decrease), Ghrelin (increase), Leptin (decrease)
ARP & NYP neurotransmitters at synapse promote hunger
Anorexigenic Neurones: What are they? What hormones affect them? What neurotransmitters/receptors are involved?
Anorexigenic neurones suppress the appetite
Leptin (increase), Insulin (increase)
αMSH (from POMC) acting at MC4 receptors promote satiety
What are Incretins?
Incretins are gut-derived peptide hormones that are rapidly secreted in response to a meal
Incretins stimulate a decrease in blood glucose levels
What are the two main incretins in humans?
Glucosedependent Insulinotropic Polypeptide (GIP)
Glucagon-Like Peptide-1 (GLP-1).
Where are GIP and GLP-1 secreted from?
They are secreted from the intestine on ingestion of glucose or nutrients
to stimulate insulin secretion from pancreatic β cells
What are GLP-1R and GIPR?
Glucagon-Like Peptide 1 Receptor (GLP-1R)
Glucosedependent Insulinotropic Polypeptide Receptor (GIPR)
Both are class B G protein-coupled receptors (GPCRs) which mediate the effects of GLP-1 and GIP respectively
