ANSC 424- 4.1 Food Intake and Pancreas

what were the different theories about the regulation of food intake?

1. Lipostatic hypothesis

2. Glucostatic hypothesis

what is the lipostatic hypothesis?

Kennedy 1953- adipose tissue produces specific lipostatic factor

what is the glucostatic hypothesis

Mayer and Thomase 1967- fluctuations of glucose/ glycemia lead to stimulation/inihibtion of food intake

what actually regulates food intake

complex homeostatic process regulated by many endocrine and metabolic factors

—> and other factors: visual, olfactory, taste sensation, emotions, memory and life conditions

what kind of hormones regulate food intake

gastrointestinal hormones

what hormones are produced by the stomach and their function?

1. ghrelin: hunger, growth hormone release

2. gastrin: acid secretion

what hormones are produced by the duodenum of SI and their function?

cholescustikinin ( CCK): gall bladder contraction, GI motility, pancreatic exocrine secretion

secretin: pancreatic exocrine secretion

GIP: incretin acvtivity

Motilin: GI motility

wha is incretin activity?

modulating glucose homeostatisis by regulating insulin and glucagon

what hormones are found in the pancreas and their function

insulin and glucagon

pancreatic polypeptide: gastric motility, satiation

amylin: glucose homeostatisis

what hormones are found in the colon and their function

GLP1: incretin activity, satiation

GLP2: GI motility and growth

oxyntomodulin: satiation , acid secretion

PYY: satiation

what nervous systems help control food intake?

1. hypothalamus: chronic and long term food intake

2. brain stem: food intake on acute regulation

what nuclei control food intake?

1. VMH: satiety center

2. lateral hypothalamus (LH) nucleus: hunger center ( lesions lead to anorexia)

3. SCN: regualtes TIMING of food intake

4. PVN and ARC: integration of signals from HPT and HPA axes

5. Vagus: satiety signals to the brain stem after ingestion of a meal ( neural regulation)

6. Nucleus tractus solitarius and PVN: connection of brainstem with hypothalamus (serotoninergic neurons)

what is the role of arcuate nucleus on food intake?

Arcuate nucleus is the center of energy homeostasis regulation - food intake, energy expenditure and nutrient partitioning

what two main types of neurons are found in ARC help control food intake

1. alpha- MSH

2. NPY neuron peptide Y

neurons receive hormonal input from peripheral organs

what is the function of alpha- MSH

⍺-MSH neurons regulate neurons that stimulate anorexia and catabolism (VMH)

—> STOP eating and energy metabolism

act upon the VMH

what is the function of NPY neurons

NPY neurons stimulate orexia and anabolism (LH)

food intake and store energy!

what is the only non anorexigenic hormone

ghrelin ( promotes eating orexia)

what is the endocannabinoids system?

Endocannabinoids: Anandamide (AEA) and 2-arachidonoylglyerol (2-AG)

what are the receptors associated with endocannabinoids

Receptors: CB1 and CB2 – GPCRs with G⍺i ( inhibitory of cAMP)

produced from the body receptor:

explain how the endocannabinoids pathway

1. promote feeding

2. increased absorption

3. metabolism

4. storage

kind of works like grehlin

what are the effects of endocannabinoids on food intake metabolism

treatment: CB1 receptor antagonist

effects: reduced food intake, decreased lipogenesis, glucose uptake, lipogenesis, anorexigenic hormones

what are the two parts of the pancreas?

1. endocrine

2. exocrine

what are the cells found in exocrine pancreas

main function is just producing digestion enzymes

Acinar cells: Secretion of digestive enzymes (proteases, amylase, lipase)

Duct cells: Secretion of NaHCO3 ( sodium bicarbonate neutralize stomach acid)

—> Secreted into duodenum

what found in encodrine pancreas

Islets of langerhans

what are the different cell types in Islets of Langerhans?

❖ α-cells: Glucagon

❖ β-cells: Insulin

❖ 𝝳-cells: Somatostatin

❖ ε-cell: Ghrelin

❖ F-cells (PP cells): Pancreatic Polypeptide

❖ Hormones secreted into blood

what are charactersitics of islets of langerhans

1. heterogeneous

2. highly vascularized

3. blood first supplies centrally located in beta cells

4. travels to peripheral alpha and beta cells

how do beta cells work

work together!

cell proliferation of b-cells?

Proliferation of β cells is minimal after 5 years of age

❖ Average lifespan of β cells – 25 years

❖ Neogenic niche at the periphery of islets – immature β cells and Transdifferentiation of ⍺ and 𝝳 cells under extreme beta-cell loss

explain relation of the different hormones in pancrease

describe structure of insulin

51 a.a. - 2 peptide chains connected by 2 disulphide bridges

what metabolizes insulin

insulin metabolized—> liver

but c-peptide metabolized in kidney

what should be used to measure insulin secretion

C-peptide

how is glucagon produced

glucagon also produced as preproglucagon processed to proglucagon to glucagon

❖ single chain (29 a.a.)

what do beta cells contain

5000-800 granules

—> Half-life – about 5 days; younger granules are deeper in the cytoplasm, but more mobile than the older granules

what happens to older granules

Older granules are degraded intracellularly – intracellular degradation of insulin!

how are insulin stabilized in granules

organized as HEXAMERS stabilized by calcium and zinc

what is the main stimulator of insulin synthesis and release

GLUCOSE

how does glucose regulate insulin secretion in beta cells

1. glucose enters beta cells through GLUT2

2. metabolized through glycolysis

3. first enzyme glucokinase

4. end product of glycolysis—> ATP

5. when high ATP to ADP ratio, inhibits the ATP sensitive potassium channel

6. exotocysis of K+ions decreased, decrease negativity of cell

7. depolarize the cell

8. stimulate voltage Ca channel

9. increase Ca in cell

10. exocytosis of insulin granules

what is the main glucose sensor in beta cells

glucokinase

what transporters regulate glucose

GLUT2 and 4

explain steps of release of insulin from beta cells

• Glucose enters the β-cell through a special transporter called GLUT2.

• Glucose is broken down via aerobic glycolysis, increasing the ATP/ADP ratio in the cell.

• The rise in ATP closes potassium (K⁺) channels, causing less K⁺ to leave the cell and depolarizing the membrane.

• This depolarization opens calcium (Ca²⁺) channels, allowing Ca²⁺ to enter the cell.

• The increased Ca²⁺ inside the cell triggers insulin release (exocytosis of insulin-containing granules).

• Calcium-activated potassium channels open, helping the membrane repolarize (reset for the next signal).

• Byproducts of glucose metabolism (like fatty acids and succinate) support insulin release and insulin production.

• Hormones like GLP-1 (from the gut) bind to their receptors and boost insulin release by increasing cAMP, which helps enhance signaling and exocytosis.

what are the neural regulations of insulin secretion

Vagus nerve ( longest nerve in our body)

—> acts as a sensory neuron and motor neuron ( provide and receive signals from peripheral organs)

explain main function of vagus nerve

Main neuronal coordinator of appetite control, digestion and metabolism

Release of acetylcholine (cholinergic) in the pancreas stimulates insulin release

POSITIVE REGULATOR OF INSULIN SECRETION