Diabetes 1 Flashcards
main use of glucose is as
brain fuel
brain accounts for
__ % of body weight
__% of basal metabolic rate
__% of whole-body glucose utilization
Brain accounts for:
2.5% of body weight
**25% **of basal metabolic rate
50% of whole-body glucose utilization
__ cannot synthesize or store glucose
brain cannot synthesize or store glucose
where does brain get glucose?
it gets a continuous supply from circulation
to maintain blood glucose concentration, we must coordinate glucose __ into circulation and __ out of circulation and into __
to maintain blood glucose concentration, we must coordinate glucose influx into circulation and efflux out of circulation and into tissues
3 sources of glucose
- intestinal absorption
- glycogenolysis
- gluconeogenesis
glycogenolysis
glycogen to glucose
gluconeogenesis
synthesis of glucose from non-carb sources
glucose metabolism pathway steps
- Glucose is phosphorylated and trapped in the cell
- Becomes glycogen
- Can become pyruvate (glycolysis) and then lactate, alanine, acetyl-Coa
- acetyl-Coa can make ketones, citrate, fatty acids (then stored as triglycerides)
3 types of cells in Islet of Langerhans (and what they secrete)
Beta-cell → insulin (70%)
Alpha-cell → glucagon (20%)
Delta and PP cells (10%)
hormone most active during:
absorptive state
postabsorptive state
hormone most active during:
absorptive state: insulin
postabsorptive state: glucagon
insulin site of action
liver
adipose
muscle
glucagon site of action
mainly liver
insulin
blood glucose conc
blood fatty acid conc
glycogen synthesis
glycogenolysis
gluconeogenesis
insulin
↓ blood glucose conc
↓ blood fatty acid conc
↑ glycogen synthesis
↓ glycogenolysis
↓ gluconeogenesis
glucagon
blood glucose conc
blood fatty acid conc
glycogen synthesis
glycogenolysis
gluconeogenesis
glucagon
↑ blood glucose conc
↑ blood fatty acid conc
↓ glycogen synthesis
↑ glycogenolysis
↑ gluconeogenesis
target tissues of insulin
liver
adipose
muscle
insulin __ blood glucose conc
insulin decreases blood glucose conc
insulin action
glucose uptake into tissues
glycolysis
glycogen synthesis
glycogenolysis (liver)
gluconeogenesis (liver & kidney)
increases glucose uptake into tissues
stimulates glycolysis
stimulates glycogen synthesis
inhibits glycogenolysis (liver)
inhibits gluconeogenesis (liver & kidney)
insulin
decreases __ concentration
reduces __ output
promotes __ deposition and __ lipolysis
increases __ synthesis and inhibits __ breakdown
insulin
decreases blood glucose concentration
reduces hepatic glucose output
promotes fat deposition and inhibits lipolysis
increases protein synthesis and inhibits protein breakdown
insulin action on the liver
main role is to inhibit
insulin action on the liver
main role is to inhibit glycogenolysis and gluconeogenesis
indirect effects of insulin on liver
decrease __ flux to liver
decrease __ secretion
indirect effects of insulin on liver
decrease free fatty acid flux to liver
decrease glucagon secretion
insulin action on adipose
less __ to be used to produce __
insulin action on adipose
less FA to be used to produce ketone bodies
what is the incretin effect?
More insulin is secreted in response to an oral glucose load than to a matched IV glucose load
the incretin effect is mediated by __ and __
the incretin effect is mediated by GLP-1 and GIP
GLP-1 is secreted by __ cells
GIP is secreted by __ cells
GLP-1 is secreted by L cells
GIP is secreted by K cells
purpose of glucose counterregulation
prevent hypoglycemia to preserve brain function
glucose counterregulation steps
- Insulin levels decrease (blood glucose 80-85)
- Glucagon is secreted (blood glucose 65-70)
- Epinephrine is secreted (blood glucose 65-70)
- Cortisol & growth hormone (blood glucose 65-70)
- Behavioral defense (blood glucose 50-55)
sources of glucose during fasting
- free glucose (extracellular fluid (ECF) and liver)
during prolonged fasting
__ becomes sole source of glucose
__ broken down to AAs to be used for __
glucose utilization by __ and __ ceases
glucose utilization by __ declines by half
__ levels rise; brain uses __ for fuel at high concentrations
during prolonged fasting
gluconeogenesis becomes sole source of glucose
muscle protein broken down to AAs to be used for gluconeogenesis
glucose utilization by muscle and fat ceases
glucose utilization by brain declines by half
ketone levels rise; brain uses ketones for fuel at high concentrations
3 counterregulatory hormones
glucagon
epinephrine
cortisol and GH
glucagon secretion is stimulated by decrease in __ levels (__ effect)
glucagon secretion is stimulated by decrease in pancreatic islet insulin levels (paracrine effect)
glucagon is secondarily stimulated by increased __ input
glucagon is secondarily stimulated by increased sympathetic input
glucagon primarily acts on __ and causes increased __ and __
glucagon primarily acts on liver and causes increased glycogenolysis and gluconeogenesis
when is epinephrine critical?
when glucagon is deficient
epinephrine is secreted from __ in response to __ signaling
epinephrine is secreted from adrenal medulla in response to CNS signaling
epinephrine stimulate __ and __ gluconeogenesis
stimulates __ glycogenolysis
epinephrine stimulate hepatic and renal gluconeogenesis
stimulates hepatic glycogenolysis
epinephrine reduces glucose uptake by __ and __
epinephrine reduces glucose uptake by muscle and fat
epinephrine stimulates __ and limits __ from pancreatic islets
epinephrine stimulates glucagon and limits insulin from pancreatic islets
cortisol and GH promote __ and reduce __ glucose utilization
cortisol and GH promote gluconeogenesis and reduce peripheral glucose utilization
which counterregulatory hormones are not critical?
cortisol and GH
gluconeogenesis
require __ (from liver and kidneys)
__ do 10-20% of glucose production
gluconeogenesis
require G6Pase (from liver and kidneys)
kidneys do 10-20% of glucose production
renal glucose production is regulated by __ and __, but NOT __
renal glucose production is regulated by insulin and epinephrine, but NOT glucagon
what is the primary glucose counterregulatory hormone?
glucagon
diabetes prevalence in US
13%
diabetes is leading cause of __ in US
diabetes increases risk of __ and __
diabetes is leading cause of blindness in US
diabetes increases risk of CVD and death
diagnosing diabetes
fasting plasma glucose __ OR
2-hour plasma glucose __ during a __ oral glucose tolerance test OR
random plasma glucose __ with symtpoms of hyperglycemia OR
HbA1c __
diagnosing diabetes
fasting plasma glucose ** ≥126 mg/dl ** OR
2-hour plasma glucose ** ≥200 mg/dl** during a 75G oral glucose tolerance test OR
random plasma glucose ≥200 mg/dl with symtpoms of hyperglycemia OR
HbA1c ≥ 6.5%
HbA1c reflects
Hemoglobin A1c reflects the average blood glucose concentration over a 2-3 month period.
HbA1c is used to
- diagnose diabetes
- monitor blood glucose control in patients with diabetes
HbA1c measures
glycated hemoglobin
what is glycated hemoglobin
hemoglobin with glucose irreversibly attached
type 1 diabetes
an autoimmune process in which β-cells are destroyed, resulting in absolute insulin deficiency (~5-10% of diabetes cases)
type 2 diabetes
characterized by insulin resistance and β-cell dysfunction, resulting in relative insulin deficiency (~90% of diabetes cases)
people with type 1 diabetes have no
beta cells
ominous octet of hyperglycemia
- decreased insulin secretion
- decreased incretin effect
- decreased glucose uptake
- increased HGP
- increased glucagon secretion
- increased lipolysis
- increased glucose reabsorption
- NT dysfunction
type 1 diabetes
age at onset
weight
family history
autoantibodies (present?)
insulin requiring
insulin sensitivity
rise of DKA
type 1 diabetes
age at onset: any, but majorty < 25
weight: typically lean but can be overweight
family history: infrequent (may be family history of autoimmune disease
autoantibodies (present?): present
insulin requiring: yes
insulin sensitivity: normal
rise of DKA: high
type 2 diabetes
age at onset
weight
family history
autoantibodies (present?)
insulin requiring
insulin sensitivity
rise of DKA
type 2 diabetes
age at onset: any, but majority >25
weight: >80% overweight/obese
family history: frequent
autoantibodies (present?): absent
insulin requiring: variable
insulin sensitivity: decreased
rise of DKA: low
