7.4. Insulin secretion and the regulation of the secretion. The effects of insulin on the intermediary metabolism. Diabetes mellitus. Flashcards
I. Basics
1. What is Intermediary metabolism?
- Metabolic steps within the cells in which the nutrient molecules or foodstuffs are metabolized and converted into cellular components and/or provide energy => it provides the appropriate energy supply for the cells and tissues.
- Energy donors: carbohydrates, fats/lipids, AAs
I. Basics
2. What are the energy donors of intermediary metabolism
carbohydrates, fats/lipids, AAs
I. Basics
3. Is the site of storage extracellular or intracellular?
INTRACELLUAR!!!
I. Basics
4. Describe the intracellular storage of amino acids
- Can be glycogenetic
- But too “valuable” because of other functions of proteins
- During breakdown, NH3 or urea is produced
I. Basics
5. Describe the intracellular storage of lipids
- Ideal storage property
- Only oxidative breakdown
- Not suitable for every tissue
I. Basics
6. Describe the intracellular storage of carbohydrate
- Appropriate for every tissue
- Bad storage properties
I. Basics
7A. What are the 3 Major players ‘’effectors’’ of the intermediary metabolism
The regulation depends on hormones produced by different endocrine organs
1. Liver: ‘’the center’’
2. Adipose tissue:
3. Skeletal muscle
I. Basics
7B. One of Major players ‘’effectors’’ of the intermediary metabolism is
“LIVER”
=> Explain
Liver: ‘’the center’’
- Gluconeogenesis can direct sources to provide glucose
(The regulation depends on hormones produced by different endocrine organs)
I. Basics
7C. One of Major players ‘’effectors’’ of the intermediary metabolism is
“ADIPOSE TISSUE”
=> Explain
- White adipose tissue: storage site of fat/lipids
- Actually the largest endocrine tissue => produces regulatory molecules
I. Basics
7D. One of Major players ‘’effectors’’ of the intermediary metabolism is
“SKELETAL MUSCLE”
=> Explain
- Largest energy consumer if we exercise
- Other energy consumers: Brain, CT, bone tissue, skin, kidney etc.
I. Basics
8. Depending of the demand
=> What are the processes that lead to elimination of transport nutrients?
- Protein synthesis
- Lipogenesis
- Glycogenesis
- Glycolysis
I. Basics
9. Depending of the demand
=> What are the processes that lead to production of transport nutrients?
- Proteolysis
- Lipolysis
- Glycogenolysis
- Gluconeogensis
I. Basics
10A. What are the 3 basic rules of the regulation of intermediary metabolism?
I. Basics - basic rules of the regulation
10B. How do we keep the plasma [glucose] at the normal level?
I. Basics - basic rules of the regulation
10C. What is the major regulator?
Insulin
I. Basics
11. Make a schematic diagram of regulation in intermediary metabolism?
II. Insulin synthesis and secretion
1. How is insulin secreted?
Insulin is secreted by β-cells in the endocrine regions of the pancreas: the islets of Langerhans.
II. Insulin synthesis and secretion
2A. How does synthesis of insulin occur?
II. Insulin synthesis and secretion
2B. How is pro-insulin processed?
- Pro-insulin is sent to the ER and folded properly, the connecting peptide (C-peptide) is cleaved, and the mature insulin + C-peptide are packaged in equal amounts in secretory granules (Golgi)
II. Insulin synthesis and secretion
3. What are the values of secretion of insulin during fasting, mixed feeding? Also the insulin content of pancreas
II. Insulin synthesis and secretion
4A. Insulin is secreted by β-cells due to a variety of factors
=> What are these factors?
II. Insulin synthesis and secretion
4B. What are the features of incretins?
- Incretins (GLP + GIP): hormones that stimulate a decrease in blood glucose levels
+) Released due to orally ingested glucose, regulates insulin release by feed- forward mechanism
II. Insulin synthesis and secretion
5. How does glucose affect the cell?
II. Insulin synthesis and secretion
6. What is the mechanism of ↑[glucose] that leads to ↑insulin secretion
II. Insulin synthesis and secretion - Pharmacological regulation of the inwardly rectifying KATP-channel
7. What should we do if the production of insulin on the β-cells is insufficient?
When the production of insulin on the β-cells is insufficient
-> diabetes (↑[glucose]).
=> Since the KATP-channels has sulphanylurea (SU)-receptors, we can use sulphanylurea to bind and close the channel
-> depolarization
-> insulin secretion
II. Insulin synthesis and secretion - Pharmacological regulation of the inwardly rectifying KATP-channel
8. What should we do if there is an overactivation of β-cells?
If there is an overactivation of β-cells, we can use diazoxide.
- It allows KATP to remain opened even when ATP is present, thereby hyperpolarizing the cell => inhibits insulin secretion
II. Insulin synthesis and secretion - β-cell mechanism
9A. Describe β-cell mechanism
II. Insulin synthesis and secretion - β-cell mechanism
9B. Describe β-cell mechanism When the cell is well supplied with energy donors?
When the cell is well supplied with energy donors:
- AMP
-> ADP -> ATP
=> insulin secretion
II. Insulin synthesis and secretion - β-cell mechanism
9C. Describe β-cell mechanism When energy donors are sufficient?
- When energy donors are sufficient ↑[AMP] (no ATP produced) AMP will also regulate AMP-kinase, which inhibits the insulin synthesis = NO INSULIN SECRETION
II. Insulin synthesis and secretion - β-cell mechanism
9D. Describe β-cell mechanism When glucose enters the cell?
- When glucose enters the cell, AMP -> ATP and ↓[AMP] = no AMP-kinase produced
=> insulin synthesis starts (with help of Ca2+-calmodulin)
=> insulin secretion
II. Insulin synthesis and secretion - Components of the β-cell regulation
10A. What are the activators in β-cell regulation?
II. Insulin synthesis and secretion - Components of the β-cell regulation
10B. What are the AAs that act as activators of β-cell regulation?
lysine, arginine, leucine
II. Insulin synthesis and secretion - Components of the β-cell regulation
10C. What is the role of incretins as activators of β-cell regulation?
Incretins: GIP (glucose-dependent insulinotropic peptide) and GLP (glucagon-like peptide) are released due to orally ingested glucose and have stimulatory effect on
insulin
II. Insulin synthesis and secretion - Components of the β-cell regulation
10D. What is the role of Glucagon as activators of β-cell regulation?
Glucagon: induces insulin by activating a Gq-protein that causes ↑[Ca2+] and thus insulin release