Diabetes Flashcards
Diabetes Mellitus
A group of disorders of glucose ______ -
A syndrome charactized by and other disturbances in _____ and ____ metabolism
Homeostasis
Chronic hyperglycemia, carbohydrate and fat metabolism
Plasma Glucose Physiology
Normal glucose homeostasis is tightly regulated by three interrelated processes:
- Gluconeogenesis =
- Glycogen synthesis, Glycogenolysis =
- Insulin mediated =
- Glucose production in the liver (and some by kidneys)
- Glucose storage (skeletal muscle and liver)
- Glucose uptake by peripheral tissue (esp skeletal muscle, fat, and liver)
Normal Fluctuations in Plasma Glucose
Absorptive State = priority is to _____ plasma glucose (prevent marked _____)
Post-Absorptive State = priority is to _____/_____ plasma glucose (prevent marked ____)
decrease (prevent marked elevation) - when we are actively absorbing food that we consume
increase/maintain (prevent marked drop)
Glucose Production Notes
- Glucose production from substances such as ____ acid
- Skeletal muscle - significant amount of glycogen to ____ muscle ______
- Liver - significant (1), so glucose in liver can be broken down and released into bloodstream to maintain levels
- Uptake by specific peripheral tissues bc these tissues can derive energy by other means such as breakdown of (1) -> so regulation in times of low blood glucose, uptake into peripheral tissues can be ______ to save glucose for tissues that can’t use fat for energy ie (1) tissue
- lactic
- drive muscle contraction
- glycogen stores
- adipose tissue, limited, central nervous tissue
Glucose Levels (Notes)
Too high lvls of plasma glucose =
Too low of lvls of plasma glucose =
So we have to keep glucose in a ______ range with normal _____ (times of feeding and in between feeding)
toxic
inadequate support of brain function
therapeutic range - normal fluctuations
Absorptive State
What Happens
- We are consuming food, digesting it, absorbing glucose through GI tract so blood glucose levels are starting to ____
The way our body deals with this (how glucose homeostasis is maintained)
- Blood glucose + amino acids is taken up by skeletal ____
- Storage of that glucose (as intracellular ____ stores) and amino acids (in form of _____)
- _____ takes up blood glucose and stores it in form of (2)
- ______ tissues takes up blood glucose and fats -> both converted to triglycerides and stored
rise
- muscle
- glycogen, proteins
- Liver, glycogen and triglycerides
- Adipose
Post Absorptive State
What happens
- To spare glucose for the _____, uptake of glucose by (3) is b____, alternatively
-
(1): key role in post absorptive state - does 2 things
- Liver will (1) and release into blood
- (1) Take up amino acids, lactic acid, energy substrates in circulation and synthesize glucose then release into blood
- Skeletal muscle, adipose tissue, liver is going to use ____ as energy instead of glucose
-
(1): key role in post absorptive state - does 2 things
- brain, skeletal muscle, fat, and liver is blocked
-
Liver
- Break down its glycogen stores
- Gluconeogenesis
- FAT
-
Liver
Plasma Glucose Physiology
During times of high glucose (after meals “_______ state”)
- _____ in Gluconeogenesis and Glycogenolysis
- Increase in tissue ______ to glucose (esp skeletal muscle and fat, mediated by insulin)
- _____ in glucose storage (_____ synthesis)
- _____ use of fat as primary energy source/_____ fat storage
“absorptive state”
- Decrease Gluconeogenesis and Glycogenolysis
- Increase tissue permeability to glucose
- Increase glucose storage (Glycogen synthesis)
- Limit use of fat as primary energy source/increase fat storage
- We shut off gluconeogenesis and glycogenolysis*
- We turn on glucose storage*
Plasma Glucose Physiology
During the fasting state (“_______ state”)
- Release of glucose from their stores (_______)
- Making new glucose (_______)
- ______ access to glucose to only those tissues that absolutely need it like the _____ (insulin level drops)
- Use of ___ as primary energy source (________)
“Postabsorptive state”
- Glycogenolysis
- Gluconeogenesis
- Limit, CNS
- fat as primary source (lipolysis)
How does glucose get in and out of the cell?
Use of (1) - Focusing on (2)
Glucose enters and exits cells via facilitated _____ (in which a protein transporter is used and concentration gradient is still needed)
Glucose transporters - Glut 1 and Glut 4 transporters
facilitated diffusion
Glut 1 Transporters
Allows glucose entry into the cell - is ______ expressed by ____ cells and is responsible for ___ levels of b_____ glucose uptake required to sustain ____ generation by all cells
(Glut 1 expression is ____ with prolonged fasting and _____ by persistent exposure to excessive glucose)
constitutively expressed by all cells, low levels of basal glucose, sustains energy
increased with fasting, decreased with hyperglycemia
Glut 4 Transporters
Expressed in (3) types of cells, is responsibe for _____ stimulated uptake of glucose
- availability of transporters entirely _____ on insulin
Cardiac, Skeletal muscle, Adipose tissue, insulin
entirely dependent on insulin
Glut 4 Transporters
Located where?
- When insulin binds to insulin receptor - (1) pathway (second messenger system) stimulates _____ of glut 4 vesicles into the plasma ____ of the cell - ___ with plasma membrane to insert themselves into membrane and take up ______
inside cell
- PI-3K Signaling pathway, exocytosis, plasma membrane - fuses with plasma membrane to insert themselves into membrane and take up glucose
Other Insulin-Mediated Effects on Cells
- Other intracellular events stimulated by insulin
- (1) Insulin stimulates enzymes necessary to convert glucose to triglycerides, protein, and glycogen
- (1) Insulin stimulates intracellular processes that consume glucose and allow cells to proliferate and grow through (1) pathway
- Glucose Storage
- Glucose as a Growth Factor, Mitogenic Activated Protein Kinase pathway (MAPK)
Glucose Homeostasis Hormones
(2)
Both produced by ______ portion of pancreas (1) cells
Insulin, Glucagon
endocrine, Islets of Langerhans
Islet of Langherhan Cells
- Beta Cells =
- Alpha Cells =
Two hormones critical for (2) states
- Secrete insulin
- Secrete glucagon
absorptive and post-absorptive state
Actions of Insulin
During times of high glucose (after meals “_____ state”)
- Gluconeogenesis and Glycogenolysis =
- Tissue permeability to glucose (esp skeletal muscle and fat) =
- Glycogen synthesis =
- Lipogenesis =
- Lipolysis =
“absorptive state”
- Decreased gluconeogenesis and glycogenolysis
- Increase tissue permeability to glucose (allows insertion of glut 4 transporters to increase permeability)
- Increase in glycogen synthesis
- Promotes lipogenesis
- Inhibits lipolysis
Shuts off gluconeogenesis and glycogenolysis, increases enzymes necessary for glycogen synthesis and lipogenesis (fat formation), inhibits enzymes for fat breakdown
Actions of Glucagon
During the fasting state (“______ state”)
- (1) Release of glucose from their stores
- (1) Making new glucose
- Limiting _____ to glucose (esp skeletal muscle and fat)
- Lipolysis =
- Lipogenesis =
Insulin and Glucagon are ______ regulated/released
“postabsorptive state”
- Glycogenolysis
- Gluconeogenesis
- Limiting access to glucose
- Promotes Lipolysis
- Inhibits Lipogenesis
Reciprocally - presence of one hormone strongly inhibits presence of the other and opposite sources of stimulation/antagonistic relationship
Classification of Diabetes Mellitus
Most Common Types
(1) B cell destruction, leads to ______ insulin deficiency
- (2) causes
(1) insulin resistance with ______ insulin deficiency
Type 1 DM - absolute insulin deficiency
- Immune mediated
- Idiopathic
Type 2 DM - relative insulin deficiency
Classification of Diabetes Mellitus
Other Types and Causes
(1) Maturity-onset diabetes of the young (1), caused by mutations in several autosomal (sex independent) genes producing defects in insulin production. Several types but tend to act like mild type 1
(1) Chronic pancreatitis, Pancreatectomy, Neoplasia, Cystic fibrosis, etc.
(1) Acromegaly, Cushing Syndrome, Hyperthyroidism, etc. .
Genetic defects of B-cell function (MODY)
Exocrine pacreatic defects
Endocrinopathies
Classification of Diabetes Mellitus
Types and Causes
(1) Cytomegalovirus, Coxsackie virus B, etc
(1) Glucocorticoids, Thyroid hormone, a-interferon, B-adrenergic agonists, Protease inhibitors, Thiazides, etc
(1) Down syndrome, Turner syndrome, Kleinfelter syndrome, etc
(1) Diabetes
Infections
Drugs
Genetic syndromes associated with diabetes
Gestational Diabetes
Classification of Diabetes (Notes)
Type 1: autoimmune _____ of pancreatic cells (sometimes just B cells, sometimes B and A cells) - leads to _____ insulin deficiency
Type 2: insulin _____ + _____ insulin deficiency
- Relative bc they? sometimes very high (measurable amount), but deficiency is insulin levels are not high enough to _____ the resistance (insulin receptors not _____ adequately)
- destruction, absolute
- resistance + relative
- still have insulin, overcome, receptors not responding adequately
Metabolic Staging of Type 2 DM
IGT = cephalic phase impairment
DM = all phase impairment
Mechanism of Hyperglycemia in Type 2 DM
(4)
Problem with insulin - either insulin is ____ or can’t _____ insulin
- When they consume food (esp carbs) - elevates plasma glucose and insulin sensitive tissues can’t take up the glucose so stays in ______ -
- ______ can’t access that glucose (doesn’t now you’re in an absorptive state) -> assumes you’re still in the ________ state where its breaking down glycogen stores and producing glucose (_______) -> so liver ______ of glucose major mechanism of hypergylcemia of diabets
Impaired insulin secretion
Increased basal hepatic glucose production
Carb absorption
Decreased insulin stimulated glucose uptake
resistant or can’t produce insulin
- bloodstream
- Liver can’t access -> assumes still in postabsorptive state -> gluconeogenesis - liver production of glucose major mechanism of hyperglycemia of diabetes
Glucose Counter-regulation
Part of autonomic response is a rise in ______ which gives you a little boost of glucose before you can consume food
- For ppl with abslolute insulin deficiency they hav a period of time where their glucagon can be very ____, but at some point their glucagon system can ____ out and alpha cells can no longer _____ and produce glucagon
- For these pts, whether they have repeated experiences of hypoglycemia or not - Hypoglycemia can be very ______ very ______ bc they no longer have glucagon response
Takeaway: for diabetics, hypoglycemia not only a complication of tx but is something that is easy to do bc body doesn’t have all the _______ responses in place
glucagon
- high, burn out, can no longer respond
- severa very quickly
Compensatory
DKA Chart
Why do you usually NOT see DKA with Type 2DM?
What happens
- Breakdown of ____
- Lack of glucose _______
- Liver thinks your ______ bc doesn’t get insulin signal so breaks down stored glycogen -> gluco_____ -> puts out alot of glucose -> osmotic _____ -> de_____ -> __ may crash dt dehydration
- Accerlated fat breakdwon causes buildup of ____ -> metabolic ____ that effects ____ function -> _____ breathing (compensation for acidosis), appears ____kalemic (from acidosis) but paradoxical bc body has pushed it out of the cells and peeing it out
- So when giving insulin, can rapidly become hypo_____
Bc not an insulin deficiency they have insulin to prevent accelerated fat breakdown
- fat
- uptake
- starving, gluconeogenesis, diuresis, dehydration -> BP may crash
- ketones -> metabolic acidosis, brain -> kussmaul breathing, hyperkalemic
- hypokalemic
Hyperosmolar Hyperglycemic Nonketotic Syndrome
Usually seen in Type __ DM
A complication with insulin resistance and a “_____“ insulin deficiency
A constellation of signs and symptoms that reflect a _____ but ____ state
Insulin levels are high enough to suppress ______ but not high enough to facilitate glucose ____ into (2)
Clinical Manifestations (4)
Type 2
“relative”
hyperglycemic but nonketotic
lipolysis, entry into muscle and fat tissue
Hyperglycema, Glucosuria, Polyuria, Polydipsia
