physiology of pancrease Flashcards
1. Where is the pancreas located in the body?
Retroperitoneal; behind the stomach.
- What is the composition of the exocrine part of the pancreas?
The exocrine part is made up of acini, constituting 99% of the pancreas volume, and it releases pancreatic juice rich in digestive enzymes and bicarbonates.
- What makes up the endocrine part of the pancreas, and what percentage of the pancreas volume does it constitute?
The endocrine part is made up of Islets of Langerhans, constituting 1% of the pancreas volume.
- Name the different cells found in the Islets of Langerhans.
- Alpha cells (produce glucagon) - Beta cells (produce insulin) - Delta cells (produce somatostatin) -
- F cells (PP cells, produce pancreatic polypeptide hormone)
- What hormone is secreted by alpha cells, and what stimulates its secretion?
Glucagon is secreted by alpha cells. It is stimulated by low blood glucose levels (hypoglycemia, below 70-80 mg/dl) and sympathetic nervous system hormones (epinephrine and norepinephrine).
- Name the inhibitors of glucagon secretion.
Hormones produced by the intestine: Cholecystokinin and Secretin.
- What are the effects of glucagon on blood glucose levels?
Increases blood glucose levels by promoting gluconeogenesis and glycogenolysis in the liver, as well as lipolysis in adipose tissue.
- What hormone is secreted by beta cells, and what stimulates its secretion?
Insulin is secreted by beta cells. It is stimulated by high blood glucose levels (hyperglycemia, above 120-130 mg/dl).
- What are the effects of insulin on blood glucose levels?
Decreases blood glucose levels by promoting glycogenesis in the liver, lipogenesis in adipose tissue, and increased glucose uptake viaGLUT-4 in adipose tissue and muscles.
- Provide an example of hormone antagonism.
Glucagon and insulin have opposing effects and exhibit antagonism.
- Provide an example of hormone synergism.
Epinephrine and norepinephrine have similar effects and exhibit synergism.
- What is permissiveness in the context of hormone interactions?
Permissiveness occurs when one hormone needs to be present for another hormone to function. An example is that thyroid hormone is required for certain types of sex hormones to cause brain development.
- What is the process of gene expression in α-cells?
Inside the DNA of α-cells, a specific gene undergoes transcription, leading to the synthesis of mRNA. mRNA is then translated by ribosomes in the cytoplasm, producing the protein proglucagon. Proglucagon undergoes modifications in the rough endoplasmic reticulum, becomes glucagon in the Golgi apparatus, and is packaged into vesicles. These vesicles release fully packaged glucagon.
- How do alpha cells respond to hypoglycemia?
Alpha cells respond to hypoglycemia by allowing glucose entry through GLUT-1 transporters. Glucose undergoes glycolysis, leading to the production of pyruvate and acetyl-CoA, which enters the Krebs cycle. NADH and FADH2 are produced, and through oxidative phosphorylation, ATP is generated in the mitochondria. This process helps increase ATP levels in the cell.
- Explain the role of K+ channels in glucose regulation.
K+ channels on the cell membrane bind ATP. With low ATP levels (resulting from low glucose), the channels close less tightly, allowing some K+ ions to exit. The cell becomes less positive, leading to less membrane depolarization. With high ATP levels (resulting from high glucose), the channels close tightly, making the cell extremely positive, causing membrane depolarization and opening of calcium channels.
- How does glucagon synthesis lead to increased blood glucose?
Specific proteins on vesicles containing glucagon and the cell membrane,linked by Ca++, facilitate fusion. This fusion releases glucagon into the blood, raising glucose levels during fasting or post-absorptive states when glucose is needed by the brain and other tissues.
- What is the role of glucagon in the liver?
Glucagon activates adenylate cyclase through a G stimulatory protein. Adenylate cyclase produces cAMP, activating protein kinase A (pkA). pkA then stimulates glycogen phosphorylase, promoting glycogenolysis (conversion of glycogen to glucose) and activates enzymes for gluconeogenesis, converting glycerol, amino acids, and odd chain fatty acids into glucose. The elevated glucose is released into the blood.
- What is the initial step in glucagon’s effect on the adipose tissue?
Glucagon activates a G stimulatory protein that binds to Adenylate cyclase on the cell membrane, resulting in the activation of the effector enzyme.
- Describe the role of Adenylate cyclase in the adipose tissue.
Adenylate cyclase, activated by glucagon, has a specific enzyme called GTPase. GTPase converts GTP to GDP, producing energy that is used to convert ATP to cAMP. cAMP then activates protein kinase A (pkA).
- What happens during Lipolysis in response to glucagon?
Glucagon-induced activation of pkA leads to the phosphorylation of hormone-sensitive lipase (HSL). Activated HSL breaks ester bonds in triacylglycerol (TAG), producing glycerol (sent to the liver) and fatty acids.
- How does glucagon affect the adipose tissue?
Glucagon promotes lipolysis in adipose tissue by activating HSL, resulting in the breakdown of TAG into glycerol and fatty acids. This process is illustrated in Figure 4.
- What is the initial step in glucagon’s effect on the myocardium?
Glucagon activates a G stimulatory protein that binds to Adenylate cyclase on the cell membrane, leading to the activation of the effector enzyme.
- What role does cAMP play in the myocardium’s response to glucagon?
cAMP, produced by Adenylate cyclase in response to glucagon, activates** protein kinase A (pkA)** in the myocardium.
- How does activated pkA influence calcium channels in the myocardium?
Activated pkA opens specific Ca++ channels in the myocardium, leading to an increase in Ca++ levels within the cells.
- What are the physiological effects of elevated Ca++ levels in the myocardium?
Elevated Ca++ levels in the myocardium increase contractility, resulting in an increased stroke volume, cardiac output, and blood pressure. Glucagon is identified as a positive inotropic agent
- Where is the pancreas located?
The pancreas is located retroperitoneally behind the stomach.
- What is the composition of the exocrine part of the pancreas?
The exocrine part is made up of Acini, constituting 99% of the pancreas volume. It releases pancreatic juice rich in digestive enzymes and bicarbonates.
- What makes up the endocrine part of the pancreas?
The endocrine part consists of Islets of Langerhans, contributing to 1% of the pancreas volume. It contains different cells, including alpha cells (produce glucagon), beta cells (produce insulin), delta cells (produce somatostatin), and F cells (PP cells, produce pancreatic polypeptide hormone).
- What is the main secretion of alpha cells?
Alpha cells secrete glucagon.
- What stimulates the secretion of glucagon from alpha cells?
Glucagon is secreted in response to low blood glucose levels (hypoglycemia, below 70-80 mg/dl), sympathetic nervous system hormones (epinephrine, norepinephrine), and hormones produced by the intestine (cholecystokinin, secretin).
- What are the effects of glucagon on blood glucose levels?
Glucagon increases blood glucose levels by promoting gluconeogenesis (conversion of glycerol, amino acids, etc., to glucose) and glycogenolysis (breakdown of glycogen to glucose) in the liver, as well as lipolysis (breakdown of triacylglycerol to fatty acids and glycerol) in adipose tissue.
- What is the main secretion of beta cells?
Beta cells secrete insulin.
- What stimulates the secretion of insulin from beta cells?
Insulin is secreted in response to high blood glucose levels (hyperglycemia, above 120-130 mg/dl).
- What are the effects of insulin on blood glucose levels?
Insulin decreases blood glucose levels by promoting glycogenesis and minor increases in protein synthesis and amino acid uptake in the liver, lipogenesis in adipose tissue, and glucose intake via GLUT-4 in muscles.
- Provide examples of hormone interactions in the pancreas.
(1) Antagonism: Glucagon and insulin have opposing effects. (2) Synergism: Epinephrine and norepinephrine have the same effect. (3) Permissiveness: Thyroid hormone is required for certain sex hormones to cause brain development.
- Explain the concept of antagonism in hormone interactions.
Antagonism refers to hormones having opposing effects, such as the relationship between glucagon and insulin in regulating blood glucose levels.
- Describe the concept of permissiveness in hormone interactions.
Permissiveness occurs when one hormone needs to be present for another hormone to function. An example is the requirement of thyroid hormone for certain sex hormones to cause brain development.
- What is the process of insulin synthesis in beta cells?
Inside the DNA of beta-cells, a specific gene undergoes transcription, leading to the synthesis of mRNA. mRNA is translated by ribosomes, producing a specific protein. The protein undergoes modifications in the rough endoplasmic reticulum, goes to the Golgi apparatus for packaging, and vesicles with fully packaged insulin, C-peptide, and amylin are released.
- How do beta cells respond to hyperglycemia?
Beta cells respond to hyperglycemia with specific glucose transporters (GLUT-2) in the cell membrane, allowing insulin-independent glucose entry. Glucose undergoes glycolysis, leading to the production of Acetyl-CoA and ATP through oxidative phosphorylation in the mitochondria.
- What role do K+ channels play in beta cells?
K+ channels on the cell membrane bind ATP, closing them. Accumulated K+ ions, due to high glucose levels, increase positive membrane potential, stimulating Ca++ channels and causing an influx of Ca++.
- Describe the process of insulin release from beta cells.
Specific proteins on vesicles containing insulin and the cell membrane,** linked by Ca++, facilitate fusion.
This releases insulin, C-peptide, and amylin** into the blood. C-peptide serves as a marker to monitor insulin levels. Excessive insulin production leads to an excess of amylin, potentially causing amyloid deposits and beta cell destruction, a common cause of type 2 diabetes.
- How does insulin affect the liver?
Insulin binds to a tyrosine kinase receptor, activating PI3K/AKT(pkB) as an intracellular messenger. In the liver (having GLUT-2 receptors), insulin promotes glycogenesis, glycolysis, and ATP production through specific glycolytic enzymes, converting glucose to pyruvate, acetyl CoA, and entering the Krebs cycle.
- What is the role of insulin in the adipose tissue?
Insulin, binding to a tyrosine kinase receptor, activates PI3K/AKT(pkB) as an intracellular messenger. This activates GLUT-4 receptors, insulin-dependent, leading to increased glucose intake. Insulin stimulates lipogenesis by converting glucose into glycerol and fatty acids, forming triacylglycerol (TAG). Additionally, insulin promotes the intake of fatty acids.
- Explain the effects of insulin on the liver.
Insulin, through its receptor, activates PI3K/AKT(pkB), leading to glycogenesis, glycolysis, and ATP production in the liver. It converts glucose to pyruvate, acetyl CoA, and enters the Krebs cycle, producing NADH, FADH2, and ATP. This is illustrated in Figure 3.
- Describe the effects of insulin on the adipose tissue.
Insulin, via its receptor, activates PI3K/AKT(pkB), stimulating GLUT-4 receptors and promoting glucose intake in adipose tissue. Insulin also induces lipogenesis by converting glucose into glycerol and fatty acids, forming triacylglycerol (TAG). The process is illustrated in Figure 4.
- What is the initial step in insulin’s effect on muscles?
Insulin binds to a tyrosine kinase receptor, leading to the phosphorylation of tyrosine residues. This activation results in the intracellular messenger PI3K/AKT(pkB) being activated.
- How does insulin influence glucose intake in muscles?
Insulin, through PI3K/AKT(pkB) activation, stimulates GLUT-4 receptors, which are insulin-dependent, leading to increased glucose intake by muscles.
- What processes are activated inside muscle cells by insulin?
Inside muscle cells, insulin activates glycolysis, involving specific glycolytic enzymes that convert glucose into pyruvate through specific types of phosphatase activity. Pyruvate is then converted into acetyl CoA, entering the Krebs cycle and producing NADH, FADH2, and ATP.
- How does PI3K/AKT (pkB) affect amino acid intake in muscles?
PI3K/AKT (pkB) increases amino acid intake in muscles by stimulating amino acid channels, especially during the ‘fed’ or absorptive state when blood levels of amino acids are high.
- What role does PI3K/AKT (pkB) play in protein synthesis in muscles?
PI3K/AKT (pkB) stimulates protein synthesis in muscles from amino acids, contributing to the increase in muscle mass during the ‘fed’ or absorptive state.
- What is the impact of PI3K/AKT (pkB) on glucose in muscles?
PI3K/AKT (pkB) converts glucose into glycogen in muscles, contributing to the storage of glucose in the form of glycogen. This is part of the overall effects of insulin on muscles, as illustrated in Figure 5.
- Where is the pancreas
The pancreas is located retroperitoneally behind the stomach.
- What is the composition of the exocrine part?
The exocrine part is made up of Acini, constituting 99% of the pancreas volume. It releases pancreatic juice rich in digestive enzymes and bicarbonates.
- What makes up the endocrine part of the pancreas?
The endocrine part consists of Islets of Langerhans, contributing to 1% of the pancreas volume. It contains different cells, including alpha cells (produce glucagon), beta cells (produce insulin), delta cells (produce somatostatin), and F cells (PP cells, produce pancreatic polypeptide hormone).
- What are the functions of alpha cells?
Alpha cells in the Islets of Langerhans produce glucagon, which is secreted when blood glucose levels are low or during hypoglycemia.
- What are the functions of beta cells?
Beta cells in the Islets of Langerhans produce insulin, which is released in response to high blood glucose levels.
- What do delta cells produce, and what is its function?
Delta cells produce somatostatin, a hormone that inhibits the secretion of both insulin and glucagon, helping regulate the balance of these hormones.
- What is the role of F cells (PP cells) in the pancreas?
F cells (PP cells) produce pancreatic polypeptide hormone, although specific functions are not detailed in the provided information.
- Describe the overview of pancreatic cells in Figure 1.
Figure 1 provides an overview of pancreatic cells, highlighting the exocrine part (Acini) and the endocrine part (Islets of Langerhans), which contains different cell types, each responsible for producing specific hormones.
- What is the primary secretion of alpha cells?
The primary secretion of alpha cells is glucagon.
- What stimuli lead to the secretion of glucagon from alpha cells?
Glucagon is secreted in response to low blood glucose levels (hypoglycemia, below 70-80 mg/dl), sympathetic nervous system hormones (epinephrine, norepinephrine), and hormones produced by the intestine (cholecystokinin, secretin).
- What are the effects of glucagon on blood glucose levels?
Glucagon increases blood glucose levels by promoting gluconeogenesis (conversion of glycerol, amino acids, etc., to glucose) and glycogenolysis (breakdown of glycogen to glucose) in the liver, as well as lipolysis (breakdown of triacylglycerol to fatty acids and glycerol) in adipose tissue.
- What is the primary secretion of beta cells?
The primary secretion of beta cells is insulin.
- What stimuli lead to the secretion of insulin from beta cells?
Insulin is secreted in response to high blood glucose levels (hyperglycemia, above 120-130 mg/dl).
- What are the effects of insulin on blood glucose levels?
Insulin decreases blood glucose levels by promoting glycogenesis and minor increases in protein synthesis and amino acid uptake in the liver, lipogenesis in adipose tissue, and glucose intake via GLUT-4 in muscles.
- Provide examples of hormone interactions in the pancreas.
(1) Antagonism: Glucagon and insulin have opposing effects. (2) Synergism: Epinephrine and norepinephrine have the same effect. (3) Permissiveness: Thyroid hormone is required for certain sex hormones to cause brain development.
- What is the initial form of insulin synthesized in pancreatic β-cells?
Insulin is initially synthesized in the rough endoplasmic reticulum (RER) of pancreatic β-cells as a larger single-chain preprohormone known as preproinsulin.
- How is proinsulin generated from preproinsulin?
The removal of preproinsulin’s signaling peptide during insertion into the endoplasmic reticulum results in the formation of proinsulin.
- Describe the composition of proinsulin.
Proinsulin consists of an A chain, a B chain, and a connecting peptide in the middle, known as the C peptide.
- What happens to proinsulin within the endoplasmic reticulum?
In the endoplasmic reticulum, proinsulin is exposed to specific endopeptidases that excise the C peptide, generating the mature form of insulin.
- What is the structure of mature insulin?
Mature insulin consists of two polypeptide chains linked by disulfide bonds.
- What is the physiological function of the C peptide?
C peptide, when insulin is secreted into the blood, is also released but has no known physiological function. It can be used as a measure of endogenous insulin production.
- How have synthetic insulin preparations been created?
Synthetic insulin preparations have been developed by altering the amino acid sequence of endogenous insulin.
- What is the primary role of insulin in blood regulation?
Insulin regulates glucose in the blood, leading to a decrease in blood glucose concentration.
- List the biological effects of insulin that increase various processes.
Increases amino acid uptake in muscle, DNA synthesis, protein synthesis, growth responses, glucose uptake in muscle and adipose tissue, lipogenesis in adipose tissue and liver, and glycogen synthesis in the liver and muscle.
- List the biological effects of insulin that decrease various processes.
Decreases lipolysis and gluconeogenesis in the liver.
- What is the unique characteristic of pancreatic β-cells?
Pancreatic β-cells are the only cells in the body that produce insulin.
- Under what condition should β-cells secrete insulin?
β-cells should only secrete insulin in response to blood glucose rising above 5 mmol/l.
- Describe the process of glucose entry into β-cells.
Glucose enters β-cells through the GLUT2 glucose transporter and is phosphorylated by glucokinase. Glucokinase acts as a glucose sensor, with a Km in the physiological range of glucose concentration. A change in glucose concentration leads to a dramatic change in glucokinase activity.
- How does increased glucose metabolism affect intracellular ATP concentration?
Increased metabolism of glucose leads to an increase in intracellular ATP concentration (36 ATP per glucose).
- Explain the role of ATP in insulin secretion.
ATP inhibits the ATP-sensitive K+ channel (KATP), resulting in depolarization of the cell membrane.
- What follows the depolarization of the cell membrane in the insulin secretion process?
Depolarization results in the opening of voltage-gated Ca2+ channels. An increase in internal Ca2+ concentration leads to the fusion of secretory vesicles with the cell membrane and the subsequent release of insulin.
- Describe the basal rate of insulin release.
Insulin is secreted at a low basal rate, accounting for about 5% of insulin produced.
- How is post-prandial insulin release patterned?
Post-prandial insulin is secreted in relation to post-meal glucose in a biphasic pattern.
- Why does the post-prandial release of insulin exhibit a biphasic pattern?
The first phase, preventing a sharp increase in blood glucose, involves the immediate release of 5% of insulin granules (readily releasable pool - RRP). The second phase, more tuned to the glucose exposure requirements, requires preparatory reactions in the reserve pool, involving signaling processes related to glucose exposure.
- What is the composition of the Islets of Langerhans?
Islets of Langerhans are clusters of approximately 1000 endocrine cells, making up 1-2% of the pancreatic volume. The remainder mostly constitutes the exocrine pancreas, which secretes digestive enzymes.
- Name the different endocrine cell types in the Islets of Langerhans.
The different endocrine cell types in the Islets of Langerhans include β-cells (secrete insulin), ⍺-cells (secrete glucagon), δ-cells (secrete somatostatin), PP cells (secrete pancreatic polypeptide), and ε-cells (secrete ghrelin).
- Describe the arrangement of β-cells and ⍺-cells in relation to blood vessels.
β-cells and ⍺-cells gather close to blood vessels, which helps them sense glucose concentration in the blood. δ-cells are found on the periphery of the islets.
- What is the role of insulin in systemic glucose homeostasis?
Insulin drives anabolic pathways in target tissues to promote the storage of nutrients and lower blood glucose levels.
- How do beta cells respond in terms of insulin secretion?
Beta cells respond to numerous nutrients and hormones, besides glucose, to coordinate insulin secretion.
- How does normal physiological compensation occur in response to increased insulin sensitivity or release?
In normal patients, increased insulin sensitivity results in a compensatory decrease in insulin secretion, and vice versa.
- What happens in T2DM concerning insulin sensitivity and release?
In T2DM, there is no compensation for decreased insulin sensitivity or release. Individuals with T2DM will no longer have a biphasic pattern of insulin secretion.
- What granule-related defects are observed in T2DM?
In T2DM, the number of secretory granules per β-cell is reduced, leading to degranulation. Insulin secretion defects are observed early in the etiology of T2DM (pre-diabetes).
What happens in alpha cells at low glucose levels?
- Glucose uptake and metabolism are low. 2. KATP channels are open. 3. Voltage-gated sodium channels (NaV) contribute to action potentials. 4. P/Q type voltage-gated calcium channels (CaV) enable calcium influx. 5. Glucagon exocytosis is triggered.
What occurs in alpha cells when glucose levels are high?
- Glucose uptake and metabolism are high. 2. KATP channels are closed, and the cell is depolarized. 3. Presence of SGLT2 glucose transporters contributes to non-voltage-regulated sodium ion influx. 4. NaV and CaV channels are closed, and glucagon is not exocytosed.
What is the primary action of glucagon?
Glucagon acts on the liver to promote hepatic glucose production, raising blood glucose levels.
How is glucagon secretion affected in T2DM, especially in the fed state?
Glucagon secretion is elevated in the fed state in T2DM and contributes to hyperglycemia.
Which hormone is secreted from δ-cells in response to nutrient or hormonal stimulation?
Somatostatin 14
What is the role of SST14 in paracrine regulation of islet function?
SST14 suppresses beta cell and alpha cell function in a paracrine manner, signaling the functional status of neighboring islet cells and modifying a cell’s activity to coordinate its hormone secretion.
What is the incretin effect?
The incretin effect refers to the greater increase in insulin production in response to oral glucose than in response to IV glucose.
Which hormone, secreted by gastrointestinal L-cells, plays a key role in the incretin effect?
GLP-1 (Glucagon-Like Peptide-1)
What are the effects of GLP-1 on beta cells?
GLP-1 increases glucose-induced insulin release by beta cells, promotes beta cell proliferation, and suppresses glucagon secretion at depolarizing glucose concentrations. It does not stimulate insulin secretion in the absence of a depolarizing stimulus (e.g., glucose).
How does GLP-1 signal its effects?
GLP-1 signals via a G protein-coupled receptor (second messenger cAMP).
How do incretin drugs act to augment insulin secretion?
Incretin drugs act via an amplifying pathway through the GLP-1/GIP receptor and cAMP to augment insulin secretion when the pathway is triggered. Therapeutic targeting of the incretin effect is achieved via DPP4 inhibition (e.g., sitagliptin) or delivery of DPP4-resistant GLP-1 analogs (e.g., liraglutide, semaglutide). As incretin drugs act via the amplifying pathway (glucose-dependent mechanism), there is no risk of hypoglycemia.
