Endocrine systems Flashcards
(21 cards)
Endocrine system
- “endo”: within “crine”: secrete
- made up of different glands/tissues
- regulation
- metabolism
- growth, development
- reproduction
- H2O, electrolyte balance
- Behavior
Receptors
- cytoplasmic/nuclear
- lipophilic hormones (steroids)
- binds hormone response element promotor on DNA-gene expression (FXR-bille acid nuclear receptor)
- Cell surface
- Hydrophiliy hormones (proteins, peptides, catecholamine)
- Ion-channels (Ca2+ control of insulin release)
- Tyrisine kinase enzyme receptor (insulin receptor)
- G Protein-coupled receptors (GPCR) (B-adrenegic sigballing)
Second messengers
- short lived intracellular signaling molecules
- high c –> rapid alterations in the activity of one/more cellular enzymes
- removal/degradation of sec. messengers –> terminate cellular response
types of secon messengers:
* hydrophylic: cAMP, cGMP, IP3, Ca2+
* hydrophobic: Diaglycerol, Pi
White adipose tissue: Structure
Subcutaneous
- Layer of adipose tissue
- Main depots: abdominal, gluteal (‘hip fat’,
peripheral obesity )
- Low risk association
- ‚female‘ type of fat distribution
Intra-abdominal
- Covers inner organs of the abdominal
cavity (central obesity)
- Risk factor: Metabolic Syndrome
- ‚male‘ type of fat distribution
White adipose tissue: function
- Energy storage: High energy content (38 kJ/g)
(Carbohydrates: 17 kJ/g) - Temperature-Isolation
- Mechanical protection
- Endocrine Organ
- Energy homeostasis
- Source of adipokines: Leptin,
Adiponectin, etc.
White adipose tissue: heterogeneity
Relative cell numbers:
Adipocytes represent only a small fraction of all cells present in adipose tissue
Fat cell (Adipocyte):
* Storage of triglycerides,
* secretion of hormones (adipokines)
* 95 % of total volume
Preadipocytes:
* regenerative reservoir
* secretion of cytokines
* 15-50 % of all cells
Immune cells:
* Macrophages, neutrophils
* B-/ T-cells
* inflammation response
Endothelial cells/ VSCMs/ blood vessels:
* Nutrient
* gas
* hormone supply
Fibroblasts/ Extracellular matrix:
* Structural component
* tissue integrity
* cell-cell-communication
* presentation of signaling molecules
White adipocytes: Morphology
Structure: Mainly (unilocular) lipid droplet
▪ Color: white/ivory
▪ Cell size: 50-150 μm
▪ Other components: peripheral nucleus, few mitochondria
▪ Blood perfusion: Arterioles (few)
Obesity
Obesity, WHO, 2013
*1.4 billion BMI > 25
*500 million BMI > 30
Obesity is a complex and multifactorial disease that develops from the interaction bewteen genotype and environment
–> abnormal or excessive fat accumulation that presents a risk to health.
energy intake excess over long peirod –> overweight, adiposity
Brwon adipose tissue
Occurrence
1. Newborns:
- Thin sheet between shoulder blades
(interscapular)
- Around adrenal glands (perirenal)
- Adults:
- Cervical: Deep neck regions (around
blood vessels)
- Supraclavicular (Collarbone)
- Paravertebral: Along upper spine and
large thoracic blood vessels
Brown adipose tissue: function
- increases energy expenditure
- Metabolizes lipids: HEAT
- Maintenance of body temperature
- Protection against cold
- Hibernation - Generation of heat 300x
more efficient than muscle - 20 % of total energy consumption
Brown adipose tissue: morphology
- high mitochondrial density: Fe-rich –> brown colour
- High UPC1 expression
- High capillary density
- Numerous small lipid droplets
Pancreas: Anatomical properties
- pancreatic duct: exocrine conduct: digestion
- Acinar cells - endocrine cells: glucose homeostasis
Islets of langerhans:
* Beta cells: production of insulin, c-peptid, amylin
* Alpha cells: glucagon secretion –> elevates blood glucose levels (–>liver)
* Delta cells: somatostatin producing cells (among other organs: stomach, intestine): regulates insuline, glucagon secretiom
* PP (gamma) cells: Pancreatic polypeptide (PP) secretion
- PP: 36AA peptide,
- regulation of pancreatic hormone secretion in
response to different stimuli (exercise, food, protein)
* Epsilon cell: Production of Ghrelin (also from other sites in the body)
- Regulation of satiety and metabolic rate
Glucose stimulated insulin secretion from β cells
glucose through GLUT-2
* accelerate metabolism of intracellular glucose
* increased cytoplasmic ATD/ADP ratio
* plasma membrane depolarization through clousre of ATP-sensitive K+ channels + Ca2+ influxthrough voltage-dependent Ca2+ channels
* increased c(ca2+)
* insulin secretion
Insulin signaling
insulin binding
* phosphorylation + activation in insulin receptors
* insulin receptor substrates (IRS) binding on phosphorylated receptor sites
* lipidkinase phosphoinositide-3-kinase biinds with regulatory domain on phosphorylated position in IRS molecule
* PIP2 –> PIP3
* PIP3-dependent protein kinase (PDK1) binds PIP3 –> active
* activation of other kinases (e.g: Akts1)
* Akts1 diffuses in cell
* signal relay
Lipotoxicity
Definition: Lipid-induced metabolic organ and tissue damage
- Occurrence: When capacities from lipid storage are surpassed (Spillover-Effect)
- Storage and metabolism mostly in adipose tissue
- Limited storage capacity in other organs leads to local cytotoxicity of lipids
Physiological mechanism of Lipotoxicity
- increase fatty acids (FFA) supply or unbalanced FFA composition (alone or in combination with high glucose)
–> stress response in pancreatic Beta cells (ER/oxidative stress with high ROS production; mitochondrial dysfunction, inflammatiom, impaired autophagic flux)
–> results: beta cells dysfunction, apoptosis, dediffrentiation
Physiological regulation of development of insulin resistance
- Fatty acids induce pro- inflammatory cytokine production via NFκB-pathway
- FFA binds to toll-like receptor 4
(TLR4) - TNFα causes insulin resistance by blocking insulin signaling
- Inhibitory serine-phosphorylation of IRS1/2
Liver
1. Portal Vein (75%): Nutrients and toxicants from intestine
2. Hepatic artery proper (25%): Oxygenated blood
*1+2 in 3
3. LIVER
1. Storage (Glycogen, Vitamins)
2. Bile production (Digestion)
3. Synthesis (Albumin)
4. Breakdown (Insulin)
5. Detoxification (Alcohol)
6. … 500 functions
4. Hepatic Vein (100%)
To heart/ lung for re-oxygenation
and distribution throughout the body
Anatomic properties of hepatic lobules
hepatocytes = workhorse of the liver
- Provides the majority of hepatic functions related to synthesis, storage, and detoxification
- 70-85% of liver parenchymal
cells (vs. non-parenchymal cells) - Regeneration of the liver (exceptional replicative capacity despite terminal differentiation) after removal of max. 75% of total liver
Liver: Bile productiona nd function
Bile acid synthesis
* Primary bile acids: Liver
* Secondary BA: Microbiota/ Colon
* Conjugation with glycine or taurine
* Cytochrome P450-mediated
Function
* Release into duodenum via common bile duct (together with pancreatic secretions)
* Main function: Emulsifier for lipids/ Micelle formation
* Hormone function: Binding to Farnesoid X receptor (FXR), a nuclear receptor that regulates bile acid synthesis and hepatic lipid metabolism
* Gallstones: Result from increased saturation of bile with cholesterol that leads to bile salt precipitation and crystal formation
Summary: The signaling pathways of the endocrine system
- The endocrine system is made up of glands that produce and secrete
hormones → chemical substances produced in the body that regulate the
activity of cells or organs. - These hormones regulate the body’s growth, metabolism (the physical
and chemical processes of the body), and sexual development and
function. - The hormones are released into the bloodstream and may affect one or
several organs throughout the body. - Several pahotlogies such as T2D, CVD and obesity, are directly related to
endocrine system dysfunction. - The signaling pathways of the endocrine system are a potential target to treat metabolic disease
