Diabetes Lec 1-3 Flashcards
diabetes mellitus is the most common metabolic disease characterized by?
hyperglycemia
T/F 1 in 4 US adults with diabetes don’t know they have it
true
what effect does overload of glucose metabolites and end products have due to diabetes?
increased oxidative and inflammatory stress, damage epithelial cells, and damage myelin sheaths
define macrovascular disease
disease of large blood vessels, including coronary arteries, aorta, and arteries in brain/limbs
define microvascular disease
disease involving small blood vessels
what are examples of microvascular diseases and which one is the most common?
retinopathy (most common), diabetic kidney disease, peripheral neuropathy, and autonomic neuropathy
what is the goal of comprehensive care?
preventing long-term macrovascular and microvascular complications in addition to glycemic control
preprandial (fasting) plasma glucose levels:
normal, prediabetic, and diabetic
n: <100
pre: 100-125
diabetes: over 126
peak postprandial (after meal) plasma glucose levels:
normal, prediabetic, and diabetic
n: <140
pre: 140-199
diabetes: over 200
Glucose is used for ATP production and building blocks for _______ and substrates for ________
biopolymers, glycosylation
A1C levels:
normal, prediabetic, and diabetic
n: <5.7%
pre: 5.7-6.5%
diabetic: >6.5%
describe how carbs are broken down into glucose in the small intestine
pancreatic a-amylase is secreted into the small intestine to breaks down polysaccharides to glucose
additionally, intestinal a-glucosidase breaks down saccharides to glucose
what are the glucose polymers?
what disaccharides do they breakdown into?
what monosaccharides to disaccharides break down into and via which enzymes?
starch and glycogen
maltose, sucrose, and lactose
maltase -> 2 glucose, sucrase -> 1 glucose + 1 fructose, lactase -> 1 glucose + 1 galactose
what are non-pharm ways of helping w/ glycemic control?
low-carb diet (not for pts w/ eating disorder or renal disease), and avoid added sugar. a-glucosidase inhibitor (for GI discomfort)
T/F GLUTs require ATP to function
false non-energy dependent
describe GLUT1
present in all tissue mediating basal glucose uptake
describe GLUT2
major transporter in intestinal, hepatic and renal cells with low affinity for glucose
describe GLUT3
major transporter on neurons with a high affinity for glucose
describe GLUT4
transporter in skeletal muscle and adipose tissue
T/F SGLTs are non-energy-dependent
false, they are energy-dependent
where do we find SGLT1? SGLT2?
what is SGLT1s role?
in intestinal and renal cells
in renal cells
actively transports glucose from the lumen into small intestine epithelial cells
how does glucose exit small intestine epithelial cells?
passive diffusion via GLUT2
glucose reabsorption occurs in the epithelial cells of?
the kidneys
SGLT2 transports ____ of glucose from the proximal tubule lumen into the epithelial cell
90%
SGLT1 transports ____ of glucose from the proximal tubule lumen into the epithelial cell
10%
glucose exits the kidney epithelial cell via passive facilitated diffusion via?
GLUT2 and GLUT1
what is the purpose of an SGLT2 inhibitor?
used for glycemic control: causes more glucose to be excreted via the urine
describe the different processes of glucose metabolism
glycolysis: glucose breakdown into 2 pyruvate molecules.
aerobic respiration: pyruvate breakdown to CO2 in Krebs cycle and oxidative phosphorylation
anaerobic respiration: pyruvate conversion to lactate
describe glycogenesis and glycogenolysis in the liver
When is glycogenesis activated?
glycogenesis: glucose is phosphorylated to become G6P, which is converted to G1P, a building block for glycogen synthesis
Activated during rest periods and by insulin in response to high glucose levels
glycogenolysis: glycogen is broken down to G6P to generate glucose for export into the bloodstream
(Liver) increased ____ indicates excessive glucose uptake. which promotes _______ and inhibits ________; glucose inhibits ________
G6P, glycogenesis, glycogenolysis, glycogenolysis
describe glycogenesis and glycogenolysis in the skeletal muscle
glycogenesis (same as liver): glucose is phosphorylated to become G6P, which is converted to G1P, a building block for glycogen synthesis (occurs at rest)
glycogenolysis: glycogen is broken down to F6P to generate ATP for energy in the skeletal muscle (occurs during exercise)
(Skeletal muscle) increased ___ indicates sufficient energy, which promotes ________ and inhibits ________; ATP inhibits _________
G6P, glycogenesis, glycogenolysis, glycogenolysis
describe lipogenesis in the liver (lipid synthesis)
glucose enters liver cell via GLUT2 and undergoes glycolysis. pyruvate is oxidized to citrate (start of lipogenesis) and is converted to acetyl-CoA, which is converted into fatty acid. Fatty acids are esterified into triglycerides, which are packaged to form VLDL for adipose tissue to take
describe lipogenesis and lipolysis in the adipose tissue
lipogenesis: VLDL and chylomicrons break down to fatty acids to go into adipocytes and convert to triglycerides. glucose also enters adipocytes via GLUT4 and undergoes glycolysis and oxidation to generate fatty acids which become triglycerides
lipolysis: triglycerides become glycerol and fatty acids which enters blood stream.
describe gluconeogenesis (glucose synthesis) in the liver and kidneys
what is it the reverse process of?
lactate, glycerol, amino acids, and fatty acids enter liver to help with forming glucose which enters the bloodstream and is taken up by the brain for ATP production
glycolysis
describe ketogenesis in the liver and adipose tissue
ketogenesis converts Acetyl-CoA into ketone bodies where they can undergo ketolysis to produce ATP
Glucose Homeostasis: Prandial State
-Nutrient absorption in the GI tract causes an increased circulating glucose level
- Glucose stimulates the release of intestinal hormones and neural stimuli to control pancreatic hormone secretion
- Total body glycolysis increases to generate energy
- The liver, skeletal muscle, and adipose tissue take up glucose for storage via increased glycogenesis and lipogenesis
- The production of glucose, fatty acids, and ketone bodies via glycogenolysis, gluconeogenesis, lipolysis and ketogenesis is decreased
.
Glucose Homeostasis: Fasting State
- Absence of nutrient absorption from the GI tract causes a decreased circulating glucose level
- Low glucose level causes the neural stimuli to stop pancreatic hormone secretion
- Glycogenolysis and gluconeogenesis increase in the liver to supply glucose
- Lipolysis and ketogenesis increase in the adipose tissue and liver to generate fatty acids and ketone bodies for energy production
- The storage of glucose via glycogenesis and lipogenesis is decreased
* Glycemic control
- Basal insulin maintaining fasting blood glucose
- Bolus insulin preventing prandial elevation and correcting acute elevation of blood glucose
.
Which of the following does not increase blood glucose? (the rest do)
a. absorption/reabsorption
b. glycolysis
c. glycogenolysis (liver)
d. gluconeogenesis
b
Which of the following does not decrease blood glucose? (the rest do)
a. glycolysis
b. glycogenesis
c. glycogenolysis (liver)
d. lipogenesis
c
what are islets of langerhans?
groups of pancreatic cells secreting insulin and glucagon which consists of A cells (glucagon) , B cells (insulin and amylin) , Delta cells (somatostatin) , PP cells (pancreatic peptide), and epsilon cells (ghrelin)
Glucagon stimulates ______ and _______ secretion
Insulin inhibits ______ secretion
Somatostatin inhibits _______, _____, and __________ secretion
Ghrelin inhibits _______ and _____ secretion
Pancreatic polypeptide inhibits ______ secretion
insulin, somatostatin
glucagon
glucagon, insulin, pancreatic polypeptide
glucagon, insulin
glucagon
Pancreatic hyperglycemic factor:
-proglucagon is cleaved to generate _________ in alpha (A) cells
-glucose _____ glucagon production by stimulating _____ and _____ secretion
-fatty acids _______ glucagon production
-amino acids ________ glucagon production
-neurotransmitters ______ glucagon secretion in response to hypoglycemia
-
glucagon
inhibits, insulin, somatostatin
inhibit
stimulate
stimulate
what is the mechanism of action of glucagon?
regulates energy delivery during the fasting state. Glucagon binds to G-protein coupled receptors on hepatocytes and increases cAMP production to to increase blood glucose levels by:
stimulating glycogenolysis
-activating gluconeogenesis
also increases blood ketone body level by limiting lipogenesis and activating ketogenesis
how does glucagon activation effect the heart and gut?
increases heart rate and force of contraction while relaxing gut smooth muscle
what are the different ways that glucagon-like peptide 1 (GLP-1) is produced?
-proglucagon cleaved to generate GLP-1 and GLP-2
-glucose and fatty acids stimulate GLP production
-parasympathetic stimulation in response to food consumption promotes GLP production
GLP-1 targets the ______, whereas GLP-2 targets the ________ and _______
pancreas, GI tract, brain
what is the mechanism of action of GLP-1?
regulates postprandial blood glucose levels with the pancreas as the major target organ. it binds to G protein-coupled receptor and increases cAMP production which increases intracellular calcium to decrease blood glucose levels by:
stimulating glucose-dependent insulin and somatostatin secretion to inhibit glucagon production
-inhibit gastric emptying and gastric acid secretion
what enzyme inactivates GLP-1?
Dipeptidyl peptidase 4 (DPP-4)
what drug classes do we use to increase the effects of GLP-1?
GLP-1 agonists and DPP-4 inhibitors
what is the mechanism of action of glucose-dependent insulinotropic polypeptide (GIP)?
regulates postprandial blood glucose level with the pancreas as the major target organ. GIP binds to G protein-coupled receptors to increase cAMP production to increase intracellular calcium to decrease blood glucose levels by:
-stimulating glucose-dependent insulin secretion to inhibit glucagon production
-prevent beta cell apoptosis and stimulate beta cell growth
-promote adipocyte differentiation and lipogenesis
what enzyme inactivates GIP?
DPP-4
Amylin is produced and stored with insulin in the ________ cells
Beta
________ stimulates Amylin production
Glucose
T/F factors affecting insulin production also affect Amylin production
True
What is Amylins mechanism of action?
-regulate appetite during prandial state by binding to G protein-coupled receptor and increases cAMP production
-decrease blood glucose levels by inhibiting glucagon production
-inhibit gastric emptying and intestinal motility, and improve satiety
Somatostatin is produced by ______ cells and endocrine cells
Delta
What factors stimulate somatostatin secretion?
Glucose, glucagon, and GLP-1
What are the 2 ways somatostatin regulates blood glucose levels?
Inhibits glucagon production via somatostatin receptor 2 (SSTR2) on ALPHA cells
Inhibits insulin production via SSTR5 on BETA cells
Somatostatin inhibits pancreatic secretion, gastric emptying, and gastric acid secretion
Pancreatic polypeptide is produced by?
PP (F) cells
Pancreatic polypeptides regulate ________ during the _______ state
Digestion, prandial
Mechanism of pancreatic polypeptides?
Bind to G protein-coupled receptors and increase cAMP production and regulates pancreatic secretions and gall bladder contraction
Ghrelin is stimulated by ______ and is produced by _______ and ________ cells
Fasting, epsilon, endocrine
Mechanism of ghrelin?
Regulate food intake by binding to G protein-coupled receptors to increase cAMP. Also induce gastric emptying and gastric acid secretion, and increase appetite
Of the following, select all that cause a decrease in blood glucose
A. Glucagon
B. Glucagon-like peptide 1 (GLP-1)
C. Amylin
D. Ghrelin
E. Somatostatin
F. Insulin
G. GIP
B, C, F, G
Of the following, which one increases blood glucose?
A. Pancreatic polypeptides
B. Ghrelin
C. Glucagon
D. GIP
E. GLP-1
C
insulin is produced by the pancreas; what is another term for describing insulin and what cells in the pancreas produce it?
pancreatic hypoglycemic factor
beta cells
Proinsulin is formed in the pancreas and is made up of?
How does it form into insulin?
single-chain polypeptides A, B, and C
A and B are cross-linked to generate insulin, leaving a residual C-peptide
T/F proinsulin does not lower blood glucose levels until it is cross-linked and cleaved into insulin
False, it has mild hypoglycemic action
what processes does BASAL insulin inhibit? when is/isn’t basal insulin released?
what is the purpose of BOLUS insulin?
glycogenolysis, gluconeogenesis, and ketogenesis
during the bodies’ fasting state, it stops after dietary glucose from meals
to decrease blood glucose levels after meals
after bolus insulin secretion, glucose enters the beta cell via ______ and undergoes ______ and __________________ to generate ATP
GLUT2, glycolysis, oxidative phosphorylation
how is the ATP generated by glucose used in the pancreas to cause insulin secretion?
ATP-dependent K channels close to cause cell depolarization via sodium entering cell. Sodium triggers voltage-gated Ca channels to open and increase intracellular Ca release. This causes insulin to be released into the plasma which is facilitated by cAMP
what drug class involving targeting potassium channels would effect insulin secretion?
what precautions should be taken if using this type of drug?
K channel blockers: a drug that inhibits K channel will increase insulin secretion into bloodstream
avoid fasting, prolonged exercise, and alcohol consumption
what drug class involving targeting cAMP would effect insulin secretion?
any drug class that increases cAMP
what is the significance of insulin binding to tyrosine kinase receptors?
it causes receptor autophosphorylation which phosphorylates downstream intracellular proteins. It activates PI3 kinase to activate AKT which drives the movement of GLUT4 containing vesicles to the cell membrane for glucose transport into the cell
what receptor does Foxo1 inhibit to prevent expression of enzymes involved in glucose and fatty acid metabolism? how does insulin play a role in this pathway?
peroxisome proliferator-activated receptor (PPAR)
insulin activates AKT which inhibits Foxo1 in order to allow gene expression for cell growth and division
what drug class targeting PPAR would be used to help with glycemic control?
what exactly does it do?
adverse reactions?
PPARy agonist
increase insulin sensitivity
edema, heart failure
which organ is reached first after insulin secretion?
the liver
The roles of insulin in the liver include:
-induce insertion of additional ______ into cell membrane to facilitate glucose transport
-promote glycogenesis and inhibit _________
-promote glycolysis and inhibit ___________
-promote lipogenesis and inhibit __________________
-promote protein synthesis and inhibit _____________
GLUT2
glycogenolysis
gluconeogenesis
fatty acid oxidation/ketogenesis
protein degradation
____________ is the main site of insulin-mediated glucose disposal
skeletal muscle
** insulin has a similar role in skeletal muscle as it does in the liver. it also promotes amino acid transport and induces translocation of ________ into the cell rather than GLUT2 as in the liver
GLUT4
__________ is the third major insulin-sensitive tissue involved in the regulation of body fuel
adipose tissue
AMP-activated protein kinase (AMPK) has what function in the liver? skeletal muscle?
It also increases the _____ sensitivity of cells
liver: promotes fatty acid oxidation while inhibiting gluconeogenesis and lipogenesis
skeletal: promotes glucose uptake and fatty acid oxidation while inhibiting protein synthesis
insulin
decreased ____ and increased ____ levels activates AMPK, which activates _______ pathways and inhibits _______ pathways
ATP, AMP, catabolic, synthetic
type 1 diabetes usually presents in childhood and results from autoimmune destruction of ___________
pancreatic beta cells
in type 1 diabetes beta cells do not produce ______ , whereas alpha cells have increased _______ production
insulin, glucagon
why are patients with type 1 diabetes at a higher risk of diabetic ketoacidosis?
fatty acids are used for energy production and ketogenesis since your body can not transport glucose into cells
what test can be used for type 1 diabetics to determine if they’re still producing insulin?
C-peptide test
describe type 2 diabetes
what happens to beta cells?
usually occurs in adulthood and results from insulin deficiency and insulin resistance
beta cells insulin secretory capacity decreases over time
which antigen is seen in type 1 diabetics but not in type 2?
human lymphocyte antigen
T/F beta cell destruction does not initially occur in type 2 diabetes
true
define gestational diabetes
-what can occur in early pregnancy?
-what can occur as pregnancy progresses?
-what can occur in late pregnancy?
-how do we treat it?
type of diabetes that results from glucose intolerance during pregnancy
-placental hormones can increase lipogenesis and beta cell proliferation
-placental hormones can increase lipolysis and insulin resistance, but inhibit glycogenesis
-in late pregnancy, glucose levels elevate and if the body can’t compensate with increased insulin secretion it can cause hyperglycemia and gestational diabetes
-manage symptoms with lifestyle modifications and insulin
identify 2 placental hormones which increase the risk of gestational diabetes:
A. Leptin
B. TNFb
C. Prolactin
D. Estrogen/Progesterone
A and D
identify 2 placental hormones which increase the risk of gestational diabetes:
A. Adiponectin
B. Lactogen
C. TNFa
D. PFK2
B and C
identify 2 placental hormones which increase the risk of gestational diabetes:
A. TNFb
B. Growth hormone
C. Ceterone
D. Corticosterone
B and D
T/F monogenic diabetes is an inherited type of diabetes
true
T/F maturity-onset diabetes of the young is caused by an autosomal recessive gene mutation (MODY)
MODY2 results from an abnormal _________ enzyme
false, an autosomal dominant gene mutation
glucokinase
how do monogenic and MODY diabetes effect someone?
they cause limited glucose-stimulated insulin secretion but not insulin resistance
secondary diabetes is caused by complications of certain conditions, what are examples of how secondary diabetes occurs?
-disease of pancreas, such as pancreatitis
-drugs that damage beta cells, interfere with insulin release, induce insulin resistance, impact glucose metabolism or cause autoimmunity
-infections that damage beta cells, such as mumps
-ethanol that is toxic to pancreas: chronic alcoholic pancreatitis
GLP-1, voltage-gated Ca channel, cAMP, PPARy, and AMPK promote or inhibit the actions of insulin secretion?
promote
a-glucosidase, SGLT-2, DPP-4, and ATP-dependent K channel promote or inhibit the actions of insulin secretion?
inhibit
