metabolism and pancreas Flashcards
Respiratory Quotient (RQ)
the ratio of the carbon dioxide produced for each oxygen molecule consumed during metabolic process.
When the respiratory quotient is high, carbon dioxide is ____ and oxygen is ____. In order word the oxygen consumption is ____.
high
low
high
Basal Metabolic Rate (BMR)
clinically measured estimate of the energy used by the body at rest under defined conditions measured as oxygen consumption and expressed in kcal /hour/square meter of body surface area
most of the energy we metabolized is converted to heat with only _____% utilized for actual work
25%
pancreatic and other hormones together with CNS help regulate intake and disposition of _____ and retrieve endogenous ____ stores during fasting
nutrients
energy
energy is measured in ____
calories
what are the 3 basic energy sources?
carbohydrates - 4 kcal/g , RQ = 1
fats - 9kcal/g , RQ = .7
proteins - 4kcal/g , RQ = .8
non-shivering thermogenesis
energy used to maintain body temperature.
its regulated by the hypothalamus/sympathetic nervous system
diet-induced thermogenesis
energy used to digest, absorb, and store nutrients
anabolism
synthesis of macromolecules from smaller organic molecules usually requiring energy from ATP
glycogenesis
glucose to glycogen ( storage of glucose)
lipogenesis
glycerol and fatty acids combined to form triglycerides
protein synthesis
protein anabolism
amino acids to protein
catabolism
breakdown or degradation of molecules
break bonds and makes ATP
two process of catabolism are:
hydrolysis
oxidation
hydrolysis
addition of water to break bond
oxidation
formation of ATP
glycogenolysis
glycogen to glucose (breakdown of stored glycogen)
lipolysis
triglycerides broken down to glycerol and fatty acids
proteolysis
protein catabolism
proteins broken down to amino acids
glycolysis
the lysis or breakdown of glucose to form 2 pyruvate molecules; anaerobic, occurs in cytosol
ketogenesis
fatty oxidation in liver that stops at last 4 carbons to form ketone bodies that are released into the blood as alternate energy source for many tissues
glut proteins
glucose transport proteins
what are the examples of glucose transport proteins, site of expression, and characteristics?
SGLUT1 SGLUT2 GLUT1 GLUT2 GLUT3 GLUT4 GLUT5
Identify the four main hormone producing cells of the pancreatic islets of Langerhans and the hormones they produce.
Alpha - glucagon
Beta - insulin
Delta - somatostatin
F (PP) - pancreatic polypeptide
Identify the main physiological factors that regulate insulin release (8)
- plasma glucose levels ( less than 50 mg/dl= no insulin secreted; greater than 250 mg/dl max is secreted)
- gastrointestinal peptide hormones (after meal, it reinforces glucose to increase insulin)
- amino acids (increase pancreatic insulin release)
- parasympathetic nervous system
- sympathetic nervous system (beta 2 increases insulin release, and alpha 2 adrenergic receptors decrease insulin release)
- stress (Epi is released and a decrease in insulin occurs)
- glucagon (increases insulin release)
- exercise (decreases insulin release)
insulin release is stimulated by which factors? (9)
hyperglycemia amino acids K+ FFA/ketoacids GIP - gastric inhibitory peptide GLP1 - glucagon like peptide 1 glucagon parasympathetic innervation (Ach Muscarinic receptor) sulfonylurea
insulin release is inhibited by which factors? (6)
hypoglycemia somatostatin exercise leptin sympathetic innervtion diazoxide drugs
Identify the major physiological actions of insulin (11)
- increase glycogenesis
- increase cellular uptake of glucose, amino acids, K+, phosphate, magnesium
- increase cellular glucose use (glycolysis)
- increase adipose tissue conversion of glucose to alpha glycerophosphate
- increase storage of fat in adipose tissue (lipogenesis)
- decrease production of ketone bodies (antiketogenic)
- decrease plasma levels of FFA and ketones
- decrease plasma amino acid levels
- suppression of appetite
- growth and development
- stimulation of sodium/K+ ATPase
insulin increases the following:
glucogenesis
protein synthesis
lipogenesis
glycolysis
insulin decreases the following:
glycogenolysis
protein degradation
lipolysis
gluconeogenesis
Identify the major physiological actions of somatostatin, and the clinical applications of this peptide.
- inhibition of insulin and glucagon secretion
- decreases GI motility, secretion, blood flow
- inhibition of release of pituitary hormones
- synthetic analogs used clinically to visualize and inhibit secretions of endocrine function
Identify the main physiological factors that regulate glucagon release. (4)
- influenced by decrease in plasma glucose levels
- fasting increases release
- ANS increase release bc of muscarinic receptors (parasympathetic)
- sympathetic increases release via beta2 receptors
what factors stimulate glucagon release (7)
hypoglycemia amino acids stress exersice GI hormones (CCK, GIP, gastrin) parasympathetic sympathetic (beta2)
glucagon release is inhibited by what factors?
hyperglycemia carbohydrates free fatty acids ketoacids insulin somatostatin GI hormones (GLP1 and secretin)
Identify the major physiological actions of glucagon. (12)
increases: glycogenolysis gluconeogenesis protein degradation lipolysis ketogenesis plasma glucose levels FFA and ketoacid plasma levels
Decreases: glycogenesis protein synthesis lipogenesis glycolysis plasma amino acid levels
Compare and contrast the insulin receptor and the glucagon receptor.
similarities:
- made by pancreatic cell
- inhibit somatostatin
- stimulate amino acids
- both are peptides
differences:
- glucagon made by alpha pancreatic cell
- insulin made by beta pancreatic cell
- reverse roles in catabolic and anabolic reactions
- what stimulates one, inhibits the other
- insulin increases use of glucose as energy source and increases storage of excess glucose
- glucagon stimulates glucose output by the liver and mobilizes energy stores and maintains plasma glucose levels between meals
- insulin activates transmembrane tyrosine kinase receptors
- glucagon receptors act through G-protein to stimulate adenylyl cyclase and increase cAMP
Identify the endocrine physiology regulating plasma glucose levels.
when glucose is high insulin is secreted. this stimulates the increased uptake of glucose. the excess glucose is converted to glycogen and stored or its converted to fat and stored in adipose tissue. the result is a decrease in blood glucose.
when blood glucose levels are low, theres a decrease in insulin secretion which causes a decrease in uptake of glucose by tissues. glycogen is broken down to glucose in the liver which release glucose in the blood. the glucose is synthesized from amino acids by the liver which releases glucose to the blood as well.
hypoglycemia (fasting) increases glucagon release as do exercise and stress
hyperglycemia decreases glucagon release
decrease in plasma FFA levels increase glucagon release
parasympathetic decreases glucagon release and increases insulin release
(muscarinic)
sympathetic decreases glucagon release and increases insulin release (beta2)
plasma glucose 250mg/dl insulin is secreted
Identify how the regulation of key metabolic enzymes produces the physiological responses to insulin and the glycemic hormones.
-glucose is taken up by pancreatic beta cells by GLUT2 and is converted to G6P by hexokinase. glucose is metabolized by beta cells to produce ATP. In beta cells, the ATP/ADP ratio is proportional to the extracellular plasma glucose level.
-gastrointestinal hormones, released after a meal, reinforce effects of glucose, increasing insulin release. GI hormones include gastrin, secretin, CCK, GLP1
after a meal, the ratio of insulin to glucagon rises by 10 due to increased insulin. this increases cellular glucose uptake and use, glycogenesis, increased adipose tissue lipoprotein lipase activity, FFA uptake and lipogenesis, increased amino acid uptake and protein synthesis
Glucagon increases activity of gluconeogenic enzymes: G6phosphatase - allows liver to export glucose, fructose1,6-bisphosphatase, phosphoenolpyruvate caboxykinase.
glucagon increases hepatic glycogenolysis by increasing activity of glycogen phosphorylase
Compare and contrast the pathophysiological events resulting in type 1 and type 2 diabetes mellitus.
type 1 DM:
low or no plasma insulin level
destruction or malfunction of beta cells and often caused by autoimmune process
type 2 DM:
insulin resistance or insulin secretion defect; reduced sensitivity to insulin
plasma insulin levels are often normal or may even by elevated early in progressions. patients often have low plasma insulin levels later in the progression of the disease
Identify gestational diabetes mellitus
found in pregnant women who have never had diabetes but have hyperglycemia during pregnancy
hormones from placenta decrease the action of mother’s insulin
insulin resistance makes it hard for mother’s body to use insulin and up to 3 times as much insulin may be required for response
affects mother in late pregnancy
if untreated can cause baby’s pancreas to make extra insulin to get rid of blood glucose
symptoms of diabetes mellitus 1 and 2
hyperglycemia polyuria polydipsia polyphagia dehydration weight loss (type 1) obesity (type 2) hyperlipedemia ketoacidosis
long term effects of diabetes mellitus
retinopathies
angiopathies
neuropathies
nephropathies
beta cell tumors
low fasting glucose <50 mg/dl
weight gain
sympathetic NS response to hypoglycemia:
-palpitations, sweating, tremors, hunger, anxiety
CNS:
-bizarre behavior, convulsions, coma
diagnosis: elevated fasting insulin and C peptide
treatment: remove tumor
- inhibit insulin secretion (diazoxide)
alpha cell tumors
tumor in pancreas causehyperglecemia
symptoms are like diabetes, however insulin should counter balance alpha tumors
what are the hormones of the pancreas
glucagon - alpha cells
insulin - beta cells
somatostatin - delta cells
pancreatic polypeptide - F cells
what cells are stimulated in high glucose
beta cells - insulin breaks down glucose
when K+ channels are opened, what happens to insulin?
inhibited - efflux of K+ causing membrane hyperpolarization
T/F a depolarized membrane secretes insulin
true - increasing ATP causes depolarization. Ca influx also stimulate insulin secretion
what natural compound increases the stimulation of insulin release
incretins - byetta pen injections is the synthetic drug made
what stimulates insulin secretion
sulfonylurea drugs (close K channels) hyperglycemia glucagon GLP1 GIP parasympathetic
what inhibits insulin secretions
diazoxide drugs (open K channels)
hypoglycemia
somatostatin
sympathetic innervations
glucose movement into cells is increased by insulin through which transport?
GLUT4 - increases the uptake of glucose into the cell
what breaks downs GLP1?
DPP4 _ drugs are used to target this enzyme to keep GLP1 around longer for type 2 diabetes
what increases the level of glucose in the body?
glucagon - opposite effect of insulin stimulation and inhibition
glycolysis, lypogenesis, protein synthesis, and glycogenesis are stimulated by?
insulin
ketogenesis, gluconeogenesis, lipolysis, protein degradation, and glycogenolysis are stimulated by?
glucagon
diabetes mellitus is the lack of what?
insulin type1- insulin dependent (destruction of beta cells)
type 2 - non-insulin dependent (reduced sensitivity to insulin)
diabetes insipidus is the lack of?
ADH
normal fasting glucose is?
less than 100 mg/dl
diabetes mellitus is classified at what glucose levels?
greater then 126 mg/dl
what type of diets affect pregnant women?
gestational diabetes - insulin resistance may be produced or exacerbated by placental hormones
someone with hypoglycemia and increased C-peptide levels have?
beta cell secreting tumor (insulin overdose would have low levels of c-peptide)
SGLUT1 site of expression
S3 segment of proximal kidney tubules intestinal mucosa (apical membrane)
SGLUT2 site of expression
S1 and S2 segments of proximal tubules (apical membrane)
GLUT1 site of expression
S2 and S3 proximal tubule basal brain RBC endothelium most other tissue
GLUT2 site of expression
S1 proximal tubule basal
liver
pancreatic beta cells
intestine basal
GLUT3 site of expression
brain
placenta
testes
GLUT4 site of expression
skeletal
cardiac muscle
fat cells
GLUT 5 site of expression
small intestine
sperm
SGLUT1 characteristics
cotransports 1 glucose and 2 Na
SGLUT2 characteristics
cotransports 1 glucose and 1 Na
GLUT1 characteristics
high affinity for glucose (not fructose)
GLUT2 characteristics
functions as glucose sensor in pancreatic beta cells
glucose entry into liver cells and beta cells are normally proportional to the glucose level in the blood
GLUT3 characteristics
primary glucose transporter in neurons
GLUT4 characteristics
- high affinity insulin-responsive glucose transporter
- up-regulated by insulin
- insulin causes insertion of GLUT4 into muscle cell plasma membrane, also activates glut4 gene so that more transporter proteins are synthesized, increasing capacity for glucose transport into muscle and adipocytes
GLUT5 characteristics
transports fructose
Anabolic reactions are usually stimulated by ___
Anabolic reactions are usually inhibited by ___
insulin
glucagon
Glucose metabolism is stimulated by ___
Glucose metabolism is inhibited by ___
insulin
glucagon
Anabolic reactions
Glycogenesis
Lipogenesis
Protein synthesis
Catabolic reactions
Glycogenolysis
Lipolysis
Proteolysis
Gluconeogenesis is stimulated by
glucagon, epinephrine, GH, and *cortisol
Gluconeogenesis is inhibited by
insulin
Glucagon-Like Peptide-1 (GLP-1)
incretin activity = ↑ insulin; ↓ glucagon; satiety activity
Ghrelin
Stimulates gastric activity, GH & appetite
A genetic defect in ____ causes maturity-onset diabetes of the young (MODY) a rare form of type 2 diabetes mellitus
glucokinase
oral hypoglycemic drugs
Sulfonylureas
Second generation sulfonylureas
Glyburide
Glipizide
Glimepride
First generation sulfonylureas
Chlorpropamide
Tolazamide
Acetohexamide
Tolbutamide
Incretins (GIP & GLP-1) stimulate ____ secretion
insulin
Only three of the twenty amino acids found in our food lead to secretion of insulin. What are they
glycine, alanine, arginine
the strongest insulin secretagogue is
arginine
Insulin release is stimulated by:
Hyperglycemia amino acids, K+, FFA\ketoacids Glucagon-like peptide (GLP-1) Glucagon Gastric inhibitory peptide (GIP) Sulfonylurea drugs Parasympathetic innervation
Insulin release is inhibited by:
Hypoglycemia somatostatin exercise leptin insulin diazoxide drugs sympathetic innervation
Anabolic reactions and Catabolic reactions:
insulin actions
anabolic: increases glycogenesis increases protein synthesis increases lipogenesis catabolic: increases glycolysis decreases glycogenolysis decreases protein degradation decreases lipolysis decreases gluconeogenesis decreases ketogenesis
During fasting conditions, several hormones act to ensure that the brain is supplied with glucose
Glucagon
Ephinephrine
Cortisol
Growth hormone
Inhibit the enzyme that breaks down the incretins GLP-1 & GIP
DPP-4 inhibitors; enhances incretin actions
DPP4 inhibitor enhances incretin actions resulting in
increase insulin
decrease glucagon
decrease apetite
examples of DPP-4 inhibitors
Sitagliptin (januvia)
Saxagliptin (Onglyza)
Linagliptin (Tradjenta)
Vildagliptin (Galvus)
Glucagon Release Stimulated by
Hypoglycemia Amino acids Stress & exercise GI hormones CCK, GIP, gastrin Parasympathetic innervation Sympathetic innervation
Glucagon Release Inhibited by
Hyperglycemia Carbohydrates Free fatty acids & ketoacids Insulin Somatostatin GI hormones GLP-1 & secretin
coupled to G proteins that stimulate adenylate cyclase
Glucagon
Anabolic reactions and Catabolic reactions:
glucagon action
Anabolic reactions:
Glycogenesis- decrease
Protein synthesis- decreases
Lipogenesis- decreases
Catabolic reactions: Glycolysis - decreases Glycogenolysis- increases Protein degradation- increases Lipolysis- increases Gluconeogenesis - increases Ketogenesis- increases
increases glycogen breakdown, glucose formation, amino acid metabolism and ketone formation by the liver
increases the breakdown of fat
glucagon
Insulin stimulates a __ that removes phosphate from the enzyme
phosphatase
Glucagon stimulates ____ which phosphorylates the same enzyme
protein kinase A
F6P to F2P6P is accomplished with ___.
the inverse is accomplished by ____
insulin
glucagon
____ stimulates facilitated diffusion out of hepatocytes:
Glucose 6-phosphatase: Glucose 6-phosphate converted to glucose
Concentration gradient favors glucose exiting the cell via ___
Glucagon
Glut-2
Diabetes Mellitus Type 2 Insulin Secretion Onset % diabetes Defect Obesity Ketosis Treatment
Non-insulin-dependent
insulin secretion: increase, Normal or decrease onset: Adulthood, Slow % diabetes: ~95% Defect: Reduced sensitivity to insulin Obesity: Yes Ketosis: Rare Treatment: Dietary control & weight reduction; oral hypoglycemic drugs, Insulin
Diabetes Mellitus Type 1
Insulin Secretion Onset % diabetes Defect Obesity Ketosis Treatment
Insulin-dependent
(lack insulin)
insulin secretion: Little or none onset: Childhood Rapid % diabetes: ~5% Defect: Destruction of beta cells Obesity: No Ketosis: Common Treatment: Insulin injections; dietary management
Acanthosis Nigricans
Benign form commonly caused by elevated insulin levels stimulating abnormal growth of skin
Types of Acanthosis Nigricans
Benign:
Insulin resistance/obesity related (IRORAN)
Medication induced
Hereditary benign
Malignant:
Cancer
Glandular disorders
Diabetes Mellitus : Long term effects of hyperglycemia
Retinopathies - major cause of blindness
Angiopathies - poor circulation, ulcerations, amputations
Neuropathies - loss of feeling, tingling sensations
Nephropathies - kidney damage & renal failure
Non-retinal visual problems - lens distortion and cataracts
Biguanides
a plant known for several centuries to reduce some symptoms of diabetes mellitus
the most commonly prescribed oral DM medication
Metformin
Drugs used to treat Type-2 Diabetes Mellitus
Oral Biguanides: Metformin Sulfonylureas: Gliburide, Glipizide Meglitinides: Nateglinide, Repaglinide Alpha-glucosidase inhibitors: Acarbose, Miglitol Thiazolidinediones: Rosiglitazone Dipeptidyl peptidase 4 (DPP-4) inhibitors: Sitagliptin, Saxagliptin, Vildagliptin Injection Insulin Incretin mimetics Amylin analogs
Macrosomia (“fat baby“) risks
risk of damage to shoulders during birth risk for breathing problems may have very low blood glucose levels at birth high risk for obesity type 2 diabetes later in life
