Term
| What are the major cells types of the pancreas? What do they do? |
|
Definition
1. acini - secrete digestive juices into the duodenum
2. α cells - secrete glucagon
3. β cells - secrete insulin and amylin
4. δ cells - secrete somatostatin
5. PP cells - secretes pancreatic polypeptide |
|
|
Term
| What is the name of groups of various types of cells in the pancreas related to blood glucose control? What is the most common cell type in this group? What is the least common cell? |
|
Definition
1. Islets of Langerhans
2. β cell
3. PP cell |
|
|
Term
| How do the cells in the pancreas regulate secretions from each other? |
|
Definition
| insulin inhibits glucagon, amylin inhibits insulin secretion, and somatostatin inhibits secretion of both glucagon and insulin |
|
|
Term
| How is insulin synthesized? |
|
Definition
| It is synthesized as preproinsulin, then cleaved to proinsulin, which is only a single chain of amino acids that is connected to itself via di-sulfide bridges; the prohormone is then cleaved, taking off the inactive C-chain, and formed into insulin; the insulin is stored in vesicles for secretion |
|
|
Term
| What kind of hormone is insulin? Steroid eicosanoid, gas, peptide, or amine derivative? |
|
Definition
|
|
Term
| What is the effect of insulin on glucose intake? Glycogen formation? Fat synthesis? |
|
Definition
| increase, increase, increase (after the glycogen stores are full) |
|
|
Term
| What is the effect of insulin on amino acid intake? Protein formation? Protein catabolism? |
|
Definition
| increase, increase, decrease |
|
|
Term
| On which cells does insulin have an especially high effect? On which cells does it have no effect? |
|
Definition
1. muscle cells, liver cells, and fat cells
2. neurons |
|
|
Term
| What substances does insulin promote the influx of besides glucose? |
|
Definition
| amino acids (especially lysine and arginine), potassium, phosphates |
|
|
Term
| How is glucose processed when it enters the cell by insulin's influence? |
|
Definition
| glucose that is meant to be stored is phosphorylated for use in metabolic processes and it is thought that glucose that is meant to be stored is put in vesicles and moved to the trans side of the cell until the insulin decreases |
|
|
Term
| What are the slower effects of insulin on cells? |
|
Definition
| over the following 10-15 minutes, insulin changes the states of enzymes due to changes in phosphorylation and even more slowly changes the transcription and translation to assist with the cell's new metabolism |
|
|
Term
| What is C-protein's effect? |
|
Definition
| It binds to ATPase and nitric oxide receptors, but its effects are unclear |
|
|
Term
| Are insulin receptors cell-surface, intracellular, or nuclear? |
|
Definition
|
|
Term
| What is the mechanism of activation of secretion for insulin? |
|
Definition
| increased [glucose] causes increase glucose influx into β cells via GLUT 2 (glucose transporters), which causes glucose phosphorylation by glucose kinase, creating glucose-6-phosphate; this molecule goes through oxidation, creating an increase in ATP, which inhibits ATP-sensitive potassium channels; inhibition of these channels causes depolarization and causes V-gated calcium channels to open, causing calcium influx, which causes exocytosis of vesicles containing insulin |
|
|
Term
| What substances can go through the process glucose goes through, effecting insulin secretion? What other hormones can cause an increase in intracellular calcium in β cells? How does the stimulus of insulin secretion compare to that of glucose? What if they are combined with glucose |
|
Definition
1. amino acids
2. glucagon, glucose-dependent insulinotropic peptide, hGH, cortisol, progesterone, estrogen, and ACh
3. The secretion effect is not as great without glucose
4. when amino acids and glucose are present in the blood, insulin secretion can double compared to just glucose |
|
|
Term
| What substances can cause the inhibition of insulin secretion? |
|
Definition
| somatostatin and norepinephrine |
|
|
Term
| What medication can cause insulin secretion? What is the mechanisms? |
|
Definition
| 1. sulfonylurea drugs (glyburide, tolbutamide) - close ATP-sensitive potassium channels, causing depolarization, causing opening of calcium channels and calcium influx, leading to insulin secretion |
|
|
Term
| What is normal fasting glucose? What is the normal rate of secretion of insulin at this level? What is the timeline for insulin secretion once there is an initial stimulus? At what blood glucose is insulin secretion rate maximized? |
|
Definition
1. about 80-90 mg/dL
2. about 25 ng/min/kg
3. levels spike within 3-5 minutes from released stored vesicles of insulin, then levels begin to drop at about 5-10 minutes from a depletion of stored vesicles, then a slow increase at about 15 minutes as new insulin is synthesized and secreted
4. about 200 mg of glucose/dL |
|
|
Term
| What is the feedback mechanism for insulin secretion regulation? |
|
Definition
| increased blood glucose causes β cells to release insulin, which causes glucose influx, which causes a drop in glucose levels, which inhibits insulin secretion |
|
|
Term
| What substances can provide an "anticipatory" rise in insulin levels? |
|
Definition
| gastrointestinal hormones such as secretin, gastrin, cholescystokinin, and G-DIP (glucose-dependent insulinotrophic peptide) |
|
|
Term
| How is insulin transported throughout the body? |
|
Definition
|
|
Term
| What is the duration of insulin? How is insulin cleared from the body? |
|
Definition
1. its half-life is about 6 minutes
2. it is degraded by most tissues, especially by insulinase in the liver |
|
|
Term
Describe the insulin receptor.
What is the mechanism of action for insulin at its receptor? |
|
Definition
1. insulin binds to a dimerized enzyme-linked receptor with 4 subunits (two α subunits that are entirely extracellular bound to two β subunits that are transmembrane
2. upon binding, the receptor autophosphorylates, causing activation of tyrosine kinase, which activates many other enzymes including insulin-receptor substrates (IRS-1, IRS-2, and IRS-3); these substrates have various effects depending on tissues, most importantly attaching glucose channels to the cell membrane |
|
|
Term
| What is the primary metabolism substrate for muscle? What can cause it to change its substrate? How is glucose used in muscles? |
|
Definition
1. fats
2. when insulin levels are high, muscle will switch to glucose as a substrate; also, during moderate to heavy workouts, muscles switch to primarily glucose as a faster energy source that fat and muscle contractions make the cells permeable to glucose even without insulin
3. glucose is either burned or stored as glycogen for later use |
|
|
Term
| What are the effects of insulin in muscle cells? |
|
Definition
| increased insulin causes an influx of amino acids, increased translation increased transcription, decreased protein catabolism, decreased gluconeogenesis |
|
|
Term
| What other hormone causes a dramatic increase in growth when combined with insulin? |
|
Definition
|
|
Term
| What is the effect of insulin in the liver? What is the mechanism? |
|
Definition
1. the liver absorbs almost 60% of the glucose in the blood after a meal
2. insulin --| liver phosphorylase, preventing glycogen breakdown while insulin is present; insulin also increase glucokinase activity which causes phosphorylation of glucose taken into the cells, leading to glucose trapping and increased glucose uptake from the blood to the liver cells; insulin also causes increased enzyme activity involved in glycogen synthesis (especially glycogen synthase, which polymerizes glucose to form glycogen) |
|
|
Term
| What happens when glycogen stores are full in the liver but insulin is still activating liver cells? |
|
Definition
| 1. glucose influx will continue and excess glucose will be made into acetyl-CoA; excess citrate and isocitrate from glucose use in the CA cycle causes acetyl-CoA carboxylase to convert acetyl-CoA into malonyl CoA, which will eventually become incorporated in triglycerides; α-glycerol phosphate (a result of glucose influx) can become glycerol, which combined with FFAs becomes TG; glycerol is much harder to make without insulin |
|
|
Term
| How is fat synthesized in the liver transported into the fat cells? |
|
Definition
| it is incorporated into VLDL and transported to fat cells; insulin increases the activity of lipoprotein lipase in the capillary walls of adipose tissue, which breaks TG into FFAs and glycerol, which can be taken into the cell and then converted back into TG |
|
|
Term
| How is the liver so important in maintaining blood glucose levels? |
|
Definition
| the liver acts as a buffer system: it takes in excess glucose after/during a meal and releases stored glucose to maintains glucose levels in the blood when glucose levels start to drop |
|
|
Term
| What occurs at the fat cells when insulin is present? |
|
Definition
| the fat cells have increased activity at lipoprotein lipase, which breaks TG into FFAs and glycerol and fat cells intake FFAs for storage |
|
|
Term
| What occurs at the fat cells when insulin is not present? |
|
Definition
| decreased insulin means increased hormone-sensitive lipase and increased hydrolysis of TG, increased FFAs in the plasma, and increased beta oxidation; fat becomes the main substrate for energy except in the brain |
|
|
Term
| What happens at the fat cells when insulin levels stay very low for long periods of time? |
|
Definition
| beta oxidation persists and excess acetyl-CoA is converted into acetoacetic acid; without insulin metabolism of this acid is decreased and the acid builds up, dropping pH, causing the increase of ketone bodies and leading to ketosis and eventually ketoacidosis, diabetic coma, and death |
|
|
Term
| What is the mechanism for the liver buffer system when glucose levels drop? |
|
Definition
| drop in glucose levels cause a drop in insulin secretion which inhibits glycogen synthase and activates liver phosphorylase, which splits glycogen into glucose-phosphate; lack of insulin also activates glucose phosphotaste, which splits glucose-phosphate into glucose and phosphate, causing glucose to diffuse into the blood |
|
|
Term
| Why does insulin not affect brain cells? |
|
Definition
| brains cells are permeable to glucose without the need of insulin and run almost entirely on glucose |
|
|
Term
| What kind of hormone is glucagon? Steroid, peptide, eicosanoid, amine derivative, or gas? |
|
Definition
|
|
Term
| What cells express the gene for preproglucagon? What cells express genes for peptides similar to glucagon, and what are those hormones? What are the functions of these latter hormones? |
|
Definition
1. hypothalamus, α-cell, and intestines
2. interstitial cells express genes for glucagon-like peptide 1 and 2 (GLP-1 and GLP-2)
3. GLP-1 helps regulate islet function and GLP-2 helps with gastric emptying and decreased GI motility |
|
|
Term
| How is glucagon synthesized? Is it stored? |
|
Definition
| it is synthsized as preproglucagon, cleaved to proglucagon, further cleaved to glucagon, and then stored in vesicles for secretion |
|
|
Term
| What is glucagon's effect on glycogenlysis? Gluconeogenesis? FFA influx and storage? |
|
Definition
| increase, increase, decrease |
|
|
Term
| What additional effects does glucagon have at high levels? |
|
Definition
| it increases the activity of adipose cell lipase, which increases FFAs in the blood and will lead to increase FFA influx and beta oxidation; high glucagon also causes increased heart contractility, increased blood flow to some tissues (including the kidneys) increased bile secretions, and inhibited gastric acid secretion |
|
|
Term
| What is the mechanism of action for glucagon? |
|
Definition
| glucagon attaches to its receptor and activates adenylyl cyclase, which increases cAMP, which activates protein kinase regulator protein, which activates protein kinase, which activates phosphorylase b kinase, which turns phosphorylase b to phosphorylase a, which degrades glycogen into glucose-1-phosphate, which will lose its phosphate and be transported into the blood, increase blood glucose |
|
|
Term
| Where is the glucagon receptor located? cell-surface, intracellular, or nuclear? |
|
Definition
|
|
Term
| If glucagon were constantly infused, how long would it take to deplete glycogen stores? What effect would glucagon have on the liver after the stores are empty? |
|
Definition
1. 4 hours
2. glucagon will activate enzymes that increase hepatic amino acid influx and increase gluconeogenesis |
|
|
Term
| What is the rate limiting step of gluconeogenesis? |
|
Definition
| the conversion of pyruvate to phosphoenolpyruvate |
|
|
Term
| How is glucagon secretion regulated? |
|
Definition
| with equilibrium at 80-90 mg/dL, decreased glucose causes increased glucagon and increased glucose causes decreased glucagon; also, increased amino acid concentration and β-adrenergic stimulation causes increased glucagon; increased amino acid concentration can be brought on by exercise |
|
|
Term
| What is steatosis? How could it affect glucagon activity? |
|
Definition
1. a fatty liver
2. higher than normal levels of glucagon can cause increased FFAs in the blood; if the liver has already filled its stores and the adipose cells have too (as in obesity), the liver will attempt to convert the FFAs into ketoacids, which can cause ketoacidosis |
|
|
Term
| What is the name for the hormone that can simultaneously decrease glucagon and insulin secretion? |
|
Definition
|
|
Term
| What kind of hormone is somatostatin? Steroid, peptide, eicosanoid, gas, or amine derivative? |
|
Definition
|
|
Term
| How is somatostatin synthesized? |
|
Definition
| the δ cells of the islets of Langerhans synthesize it as preprosomatostatin, cleave it to prosomatostatin, and then to somatostatin; somatostatin is also made in the hypothalamus (in the same manner) |
|
|
Term
| What is another name for somatostatin? Why is it called that? |
|
Definition
1. growth hormone inhibitory hormone
2. it is released by the hypothalamus to suppress somatotrope activity |
|
|
Term
| What is the duration of somatostatin? |
|
Definition
| 1. its half-life is about 3 minutes |
|
|
Term
| What causes the secretion of somatostatin? |
|
Definition
| increased glucose, increased amino acids, increases FFAs, and increase in the secretion of several gastrointestinal hormones |
|
|
Term
| What is the function of somatostatin? |
|
Definition
| it decreases insulin and glucagon secretion, decreases the motility of the stomach and duodenum, decreases the secretion of the gallbladder, and decreases the secretion and absorption of the GI; overall, this is thought to extend the period of time the food stays in the GI for efficient absorption and processing |
|
|
Term
| What feedback loop occurs with severe hypoglycemia? Prolonged hypoglycemia? |
|
Definition
1. decreased glucose stimulates the hypothalamus to stimulate the sympathetic nervous system to release epinephrine, which increases glucose release
2. prolonged decreased glucose levels cause cortisol and hGH secretion, which causes a decrease of glucose utilization in non-brain cells, which helps maintain glucose levels |
|
|
Term
| What can excessive hyperglycemia cause? Prolonged hyperglycemia? |
|
Definition
1. excess glucose levels cause an increase in osmotic pressure, which causes cellular dehydration; excess glucose levels also cause loss of glucose in the urine, which will lead to osmotic diuresis
2. damage to many tissues, including blood vessels and nerves |
|
|
Term
| What is diabetes mellitus? What is Type 1? What is Type 2? |
|
Definition
1. a syndrome in which there is impaired carbohydrate, fat, and protein metabolism
2. metabolism dysfunction due to a lack of insulin secretion
3. metabolism dysfunction due to a decrease in tissue sensitivity to insulin |
|
|
Term
| What is the cause of diabetes mellitus type 1? |
|
Definition
| 1. an injury to or degradation of the β cells; may because caused by viral or autoimmune issues, but genes seem to play a large role in the susceptibility of β cells to degradation |
|
|
Term
| What is the usual age of onset of IDDM? What percentage of people with DM have IDDM? |
|
Definition
|
|
Term
| What are the stages of IDDM onset? |
|
Definition
| increased plasma glucose, increase FFA utilization, increased formation of cholesterol, and increased protein catabolism |
|
|
Term
| What initial problems can IDDM cause (not due to chronically high glucose levels)? |
|
Definition
| decreased insulin causes decreased glucose influx meaning increased plasma glucose, which causes increased glucose lost in the urine; increased plasma glucose also causes increase osmolarity, which causes loss of water from cells and glucose in the urine causes osmostic diuresis which leads to dehydration, increased thirst, and increased ADH (because of the increased plasma osmolarity) |
|
|
Term
| What can chronic high plasma glucose cause? |
|
Definition
| chronic high [glucose] can cause damage to blood vessels which could lead to heart attack, stroke, end-stage kidney disease, retinopathy and blindness, ischemia, and gangrene; chronic high [glucose] can also cause peripheral neuropathy, ANS dysfunction, inpaired CV reflexes, impaired bladder control, decreased sensation in the extremities, and other symptoms; chronic high [glucose] can also cause kidney damage, resulting in protein in the blood and increased blood pressure due to descreased renal function; chronic high [glucose] can also cause unintended glycation of proteins leading to decreased functionality of some proteins including reduced flexibility of RBCs |
|
|
Term
| What can chronic reduced glucose influx by cells cause? |
|
Definition
| decreased glucose utilization by cells leading to increased fat and protein utilization; protein utilization will lead to muscle wasting and increased fat utilization will lead to TG breakdown, increased [FFA], and β oxidation; excess processing of FFAs in the liver can lead to a rise in keto acids which will drop plasma pH; this combined with dehydration can cause a marked drop in plasma pH and lead to diabetic coma and death |
|
|
Term
| How does chronic reduced glucose influx affect the respiratory system? |
|
Definition
| chronic reduced glucose influx eventually leads to production of keto acids and a drop in pH; a drop in pH activates chemoreceptors, which signal the respiratory centers of the brain, which cause increases breathing at rest, which causes a rise in pH, a drop in CO2, and a loss of HCO3- |
|
|
Term
| What plasma concentrations are different in diabetic coma patients? When does diabetic coma usually set in? |
|
Definition
1. severely high glucose and ketoacids, very low HCO3-, and low cations and Cl-
2. diabetic coma usually sets in when the patient's pH drops below 7 |
|
|
Term
| What is the most common form of diabetes? When is the usual onset? |
|
Definition
1. Diabetes type 2
2. Usually after 30 and it used to be mostly in patients from 50-60, but now there is an increase in cases of patient under 20 |
|
|
Term
| Which type of diabetes was referred to as juvenile diabetes? |
|
Definition
|
|
Term
| How is diabetes type 2 related to obesity? |
|
Definition
| increased fat causes the body to fill in fat stores; when there is additional fat to store after that, the body converts other tissues into fat stores; increased fat deposition in what would otherwise not be fat stores may decrease insulin signal pathways |
|
|
Term
| What is the signature symptom of NIDDM? What other symptoms does it cause? |
|
Definition
1. insulin resistance
2. high plasma glucose, preference of protein and fat metabolism, possible blood vessel, renal, and nerve damage with chronic high glucose levels, etc |
|
|
Term
| What is metabolic syndrome? |
|
Definition
| a cascade of disorders that lead to NIDDM: obesity (especially with the accumulation of abdominal fat), insulin resistance, fasting hyperglycemia, increase TG, decreased HDL, hypertension; all of these are related to abdominal fat accumulation and the predisposition to CV disease |
|
|
Term
| What are possible causes of insulin resistance? |
|
Definition
| obesity, excess glucocorticoids, excess hGH, pregnancy, polycystic ovary disease, lipodystrophy, autoantibodies to the insulin receptor, mutations in the insulin receptor, mutations of the peroxisome proliferators' activator receptor γ (PPAR γ), mutations that cause genetic obesity (melanocortin mutations), and hemochromatosis |
|
|
Term
|
Definition
| administration of insulin to return metabolisms to normal; insulin regimens depend on severity, patient, and diet; many patients are given an extended-release insulin once per day and a short-acting insulin before meals; patients may also need statins to counteract increases in plasma cholesterol |
|
|
Term
| Where does synthetic insulin come from? Where did it used to come from? Why is the latter no longer used? |
|
Definition
1. from genetically modified E. Coli, which have the human insulin gene implanted in their genome
2. insulin used to come from animals
3. patients developed a resistance to it and bacteria-made insulin is much more cost-effective now |
|
|
Term
| How does one treat NIDDM? |
|
Definition
| for many patients, exercise, caloric restriction, weight reduction, and changes in glycemic indices of food can effectively treat and even cure them; more severe cases (or less compliant patients) may require thiazolidinediones to increase insulin sensitivity and reduce liver glucose production or sulfonylureas to release additional insulin; with severe type 2 patients, insulin may be administered to control plasma glucose as other drugs may not be enough of pancreatic cells may be worn out; patients may also need statins to counteract increases in plasma cholesterol and loop diuretics to protect the kidneys from damage by excess glucose |
|
|
Term
| How does one diagnose IDDM? |
|
Definition
| loss of glucose in urine, high fasting glucose, low insulin levels, and a glucose tolerance test will reveal significantly raises [glucose] that will not fall for 4-6 hours; patients will also have acetone breath and lose keto acids in the urine |
|
|
Term
| How does one diagnose NIDDM? |
|
Definition
| patients will have high fasting glucose, high insulin levels, and a glucose tolerance test will reveal significantly raised blood glucose and levels will not fall for 4-6 hours; patients with severe type 2 will have acetone breath and loss of glucose and keto acids in their urine |
|
|
Term
| What is an insulinoma? What can it cause? |
|
Definition
1. an insulin-producing tumor in the islet of Langerhans
2. greatly increased insulin production can result in severe hypoglycemia and a reduction of glucose available to the CNS, which can lead to nerve damage and insulin shock |
|
|
Term
| How is a patient with an insulinoma treated? |
|
Definition
| either large doses of glucose or an administration of glucagon or epinephrine to start gluconeogenesis |
|
|
Term
| What does hypoglycemia cause in the CNS? What is insulin shock and what does it cause in the CNS? |
|
Definition
1. a drop of glucose below 70 mg/dL can cause the CNS to become excitable and patients may experience nervousness, have trembles, break out into a sweat, or even hallucinate
2. insulin shock is a drastic drop of glucose; at 20-50 mg/dL, at which patients may have clonic seizures and a loss of consciousness; below that, seizures stop and the patient slips into a coma |
|
|
Term
| How can the proliferation of oxidative nitrogen and oxidative oxygen affect diabetes? |
|
Definition
| when there are more oxidants than antioxidants, certain proteins and cells can be damaged; this may be one cause of diabetes |
|
|
