GLUCOSE HOMEOSTASIS AND FUEL METABOLISM Flashcards
Glucose homeostasis
Glucose homeostasis reflects a balance between __________ and ____________
hepatic glucose production
peripheral glucose uptake and utilization.
Glucose homeostasis
______ is the most important regulator of this metabolic equilibrium, but neural input, metabolic signals, and other hormones (e.g., _______) result in integrated control of glucose supply and utilization.
Insulin
glucagon
Plasma glucose concentration
Fasting blood glucose:
Random blood glucose:
Post-prandial blood glucose:
70-110mg/dl( 3.9-6.1mmol)
<140mg/dl (<7.8mmol/l)
<140mg/dl (<7.8mmol/l)
Hepatic glycogen stores : sufficient to maintain plasma glucose levels for approximately _______
This time period can be shorter if glucose demand is increased by ———- or if glycogen stores are depleted by______ or ______
8hours
exercise
illness or starvation
Systemic glucose balance
Maintenance of the normal plasma glucose concentration is accomplished by-
A network of __________
_________ signals
_________ effects
that regulate endogenous glucose production and glucose utilization by tissues other than the _____
hormones
Neural
Substrate
brain
Hormonal regulation of glucose homeostasis
List 6
Insulin
Glucagon
Thyroxine
Epinephrine
ACTH
GH
Insulin
Insulin is a polypeptide hormone produced by the _____ cells of the ______
Its metabolic effects are ____bolic and favoring ________ of ______,______,_____
β; islets of Langerhans
ana
synthesis of glycogen, triacylglycerols, and protein
Insulin
Insulin is composed of _____ amino acids arranged in ____ polypeptide chains, designated ____ and ____, which are linked together by __________
51; two
A and B
two disulfide bridges
_________ and _________ insulin differ from human insulin at _____ and ____ amino acid positions, respectively.
Pig (porcine) and beef (bovine)
one and three
Pig (porcine) and beef (bovine) insulin
Each can be used in humans for the treatment of ______; however, _________ to these foreign proteins can develop
diabetes
antibodies
Regulation of insulin secretion
Stimulation of insulin secretion by
Glucose:
•_______________ of _____________ leads to a rise in blood glucose, which is a signal for increased insulin secretion
Amino acids:
_______ of _____ causes a ____ rise in plasma amino acid levels, which, in turn, induces the immediate secretion of insulin.
Gastrointestinal hormones
intestinal peptides ________ and _________ increase insulin secretion in response to _______, and so are referred to as “_____.”
Ingestion of glucose or a carbohydrate-rich meal; insulin
Ingestion of protein; transient
cholecystokinin and gastric-inhibitory polypeptide; oral glucose
incretins
Inhibition of insulin secretion
The synthesis and release of insulin are decreased when:
-scarcity of _______
-during periods of _____ (for example, _______ or ________).
These effects are mediated primarily by _________
dietary fuels
stress
fever or infection
epinephrine
__________ is the key regulator of insulin secretion by the pancreatic beta cells
Glucose
Glucose levels >___ mmol/L (______mg/dL) stimulate insulin synthesis
3.9; 70
Glucose stimulation of insulin secretion begins with its transport into the ______ by the __________ transporter
beta cell
GLUT2 glucose t
Insulin promotes _______ glucose uptake and utilization, and inhibits ___________ as well as __________
peripheral
gluconeogenesis as well as glycogenolysis.
Role of other hormones
Epinephrine:
Secreted by ________ and _____eases blood glucose level
Acts on _____________ to bring _________ by _______________activity
Secreted in response to ____,_______, or __________
adrenal medulla; incr
both muscle and liver
glycogenolysis; increasing phosphorylase
stress, trauma, or extreme exercise.
Role of other hormones
Epinephrine:
Epinephrine has a direct effect on energy metabolism, causing a rapid mobilization of energy-yielding fuels, including glucose from the ______ (produced by ________ or -_______)
liver
glycogenolysis or gluconeogenesis
Role of other hormones
Thyroxine:
Hormone of ________
________ blood glucose level by stimulating _______ glycogenolysis and gluconeogenesis
thyroid gland
Elevates
hepatic
Role of other hormones
Glucocorticoids:
Hormones of _______
Stimulate ______ metabolism and ____ease gluconeogenesis
Inhibits glucose ______ by ________ tissues
____eases blood glucose level
adrenal cortex
protein; incr
utilization; extrahepatic
Incr
Role of other hormones
Growth Hormone and adrenocorticotropic hormone (ACTH):
Hormones of ____________
causing _____glycemia
Glucose uptake by certain tissues is ____eased by GH
ACTH decreases glucose ______
anterior pituitary gland
hyper; decr
utilization
In the early fasting state
The peripheral cells switch to __________, such as _________ and ___________
alternative fuels
fatty acids and ketone bodies.
In the early fasting state
Ketone bodies are synthesized by the _____ but utilized in the _______ cells.
Glycerol and amino acids released form the _________ and _________ respectively are used for glucose production.
________is the main fuel for brain.
TAG ________ is decreased in adipose tissues
liver; peripheral
adipose tissue and muscle
Glucose; synthesis
Role of insulin in the fasting state
low insulin levels increase glucose _________ by- Promoting hepatic _________ and ________ and Reducing glucose ——- in insulin-sensitive tissues (______ and ______)
production
gluconeogenesis and glycogenolysis
uptake
skeletal muscle and fat
Role of insulin in the fasting state
Low insulin levels promotes mobilization of stored precursors such as ________ and _________ (lipolysis).
These effects are mediated by________.
amino acids and free fatty acids
Glucagon
Role of glucagon in the fasting state
• Glucagon,secreted by pancreatic _____ cells when blood glucose or insulin levels are (low or high?) , (inhibits or stimulates?) – Glycogenolysis,
alpha; low
Stimulates
Role of glucagon in the fasting state
• Gluconeogenesis by the ______ and _____ and Prevents glucose uptake by the _______
liver and renal medulla
peripheral cells
Glucose homeostasis in well fed state
In the well fed state, glucose absorbed from gut is supplied to all cells
it acts as a signal for the release of ____ from Beta cells of pancreas
it is ______ completely to provide energy
the surplus is stored as _____ in ———- and _______
_________ obtained from pyruvate, can be used for lipogenesis, the triglycerides are stored in ___________
insulin; oxidized
glycogen
liver and muscle.
Acetyl co A; adipose tissue.
Postprandial glucose homeostasis
Postprandially, the glucose load elicits a (rise or fall?) in insulin and (rise or fall?) in glucagon, leading to a reversal of these processes.
The major portion of postprandial glucose is utilized by _________, an effect of ______- stimulated glucose ______.
Other tissues,most notably the ———, utilize glucose in an insulin-independent fashion.
Rise ; fall
skeletal muscle; insulin; uptake
brain
Glucose metabolism:
Increased ________ of glucose
Increased glycogen ______
Increased activity of the ________ pathway
Increased __________
Decreased __________
phosphorylation
synthesis
hexose monophosphate
glycolysis
gluconeogenesis
In post absorptive phase
Glucose utilization is _____eased in the _______,________, and _________
_________________ provides the most glucose (75%)
______________ providing the remainder
The glucose-_______ cycle becomes active.
___-____% of glucose is consumed by the brain
decr
liver, muscle and adipose tissue
Liver glycogenolysis
gluconeogenesis
alanine
50-60
In the state of starvation
_____________ cycle is active.
______ and ______ released from muscle are used in _____ and _____ respectively for glucose production
Glucose alanine
Alanine and glutamine
liver and kidney
In the state of starvation
________ play a central role in prolonged starvation, replacing _____ as the primary fuel for the brain and signaling a ________ in protein catabolism and alanine output from muscle.
Ketones
glucose
reduction
Variations in blood glucose levels
A) Hypoglycemia-
Decrease in blood glucose below the normal (______mg/dl) is called hypoglycemia.
A decrease in _____ secretion is the first defense against hypoglycemia.
<45
insulin
Variations in blood glucose levels
A) Hypoglycemia-
As plasma glucose levels decline just below the physiologic range, glucose counter regulatory (plasma glucose–raising) hormones are released.
Among these, pancreatic ___ cell ______, which stimulates ____________, plays a primary role.
α; glucagon
hepatic glycogenolysis
_______ is the second defense against hypoglycemia
Glucagon
Variations in blood glucose levels
A) Hypoglycemia-
Adreno- medullary ________, which stimulates ____________________ (and ——————-), is not normally critical, however, it becomes critical when ________ is deficient.
epinephrine
hepatic glycogenolysis and gluconeogenesis
renal gluconeogenesis; glucagon
_________ is the third defense against hypoglycemia.
Epinephrine
Variations in blood glucose levels
A) Hypoglycemia-
When hypoglycemia is prolonged, ______ and ______ hormone also support glucose production and limit glucose utilization.
cortisol and growth
Hypoglycemia is a laboratory ‘diagnosis’ which is usually considered a blood glucose level below _____mg/dL.
Symptoms begin at plasma glucose levels in the range of ____ mg/dL and Impairment of brain function at approximately ____ mg/dL.
60
60
50
Types of hypoglycemia
Spontaneous hypoglycemia in adults is of two principal types:
1) Fasting hypoglycemia:
Observed in patients with ________ and __________
it is often ________ or ________ and usually presents with _________ as its principal manifestation.
pancreatic beta cell tumor and hepatocellular damage
sub acute or chronic
neuroglycopenia
Types of hypoglycemia
• Spontaneous hypoglycemia in adults is of two principal types:
Postprandial hypoglycemia:
•________ hypoglycemia with ____________ insulin secretion following ______
It is relatively _____ and is often heralded by symptoms of __________________________ (sweating, palpitations, anxiety, and tremulousness).
Reactive; an elevated; a meal
acute
neurogenic autonomic discharge
Types of hypoglycemia
3)Insulin-induced hypoglycemia:
Hypoglycemia occurs frequently in patients with ________ who are
receiving insulin treatment
diabetes
Alcohol is metabolized in the liver by _____________ reactions
Ethanol is first converted to _______ by _______________.
And that is subsequently oxidized to ______ by _________________.
In each reaction, electrons are transferred to ______, resulting in a massive increase in the concentration of __________.
two oxidation
acetaldehyde; alcohol dehydrogenase
acetate; aldehyde dehydrogenase
NAD+; cytosolic NADH
Hypoglycemia and alcohol
intoxication:
Alcohol is metabolized in the liver by two oxidation reactions
In each reaction, electrons are transferred to NAD+, resulting in a massive increase in the concentration of cytosolic NADH.
The abundance of NADH favors the reduction of __________ to _______ and of _________ to ________
Thus, the ethanol-mediated increase in NADH causes the intermediates of _________ to be diverted into alternate reaction pathways, resulting in the decreased ______________.
This can precipitate hypoglycemia, particularly in individuals who have _________________________.
pyruvate to lactate
oxaloacetate to malate
gluconeogenesis; synthesis of glucose
depleted their stores of liver glycogen
Common causes of hypoglycemia
Physiological- ________ or ________
Pathological
Pronged fasting or starvation.
Fasting hypoglycemia
Drug induced- _____, oral hypoglycemic drugs,_____,__________ etc.
Critical illnesses - ______,_______, or _____ failure, and _____.
Hormone deficiencies-_____,_______, or both, _______ and _______ (in insulin-deficient diabetes)
• Endogenous __________
• Insulinoma
Insulin; alcohol; sulfonamides
Hepatic, renal, or cardiac ; sepsis
Cortisol, growth hormone
Glucagon and epinephrine
hyperinsulinism
Fasting hypoglycemia
Autoimmune (_______ to ______ or ________)
_______ insulin secretion
————— hyperinsulinism and Inherited ___________
autoantibodies
insulin or the insulin receptor
Ectopic
Congenital
enzyme deficiencies
Postprandial (reactive) hypoglycemia
Causes
Alimentary (____________)
Hereditary _____________
______________
Idiopathic.
Post-gastrectomy
fructose intolerance
Galactosemia
Hyperglycemia
Causes of hyperglycemia
_________________
Diseases of pancreas ( ________,_______,______,________ )
Infections and ————
__________
_____________
Diabetes mellitus
pancreatitis, hemochromatosis, carcinoma head of pancreas, Cystic fibrosis
sepsis
Anesthesia
Asphyxia
Hyperglycemia
Causes of hyperglycemia
Hormonal tumors- ______ ,_____,_____, and ————-
Pharmacologic agents (_______,______,______, and ————- )
Liver disease (______,________)
Muscle disorders (______________)
Adipose tissue disorders ( ————- and ___________ )
Acromegaly, Cushing’ssyn, Glucagonoma and Pheochromocytoma
corticosteroids, sympatho mimetic drugs, thiazide diuretics and niacin
cirrhosis, hemochromatosis
myotonic dystrophy
Lipodystrophy
truncal obesity
Clinical implication of disturbed glucose homeostasis- GLYCOSURIA
Although normal urine contains virtually ____ sugar but under certain circumstances, glucose or other sugars may be excreted in urine.
This condition is called ‘_____’.
no
Melituria
The term Glucosuria, Fructosuria , Galactosuria, Lactosuria and Pentosuria are applied specifically for urinary excretion of glucose, fructose, galactose, lactose and pentose respectively.
T/F
T
Glycosuria (Glucosuria) can be classified in to two main groups
A)_________ glycosuria
B)_____ glycosuria
Hyperglycemic
Renal
Hyperglycemia glycosuria
________ Glycosuria
_______ Glycosuria
Alimentary
Emotional
Hyperglycemia glycosuria
Alimentary Glycosuria(Excessive _________________ )
Emotional Glycosuria(Excessive __________)- Stress, anxiety etc.
ingestion ofcarbohydrates
catecholamine release
Hyperglycemia glycosuria
• Glycosuria due to endocrinal disorders e.g.
List 6
Diabetes Mellitus
Hyperthyroidism
Epinephrine hyper secretion
Hyperactivity of anterior pituitary(Acromegaly)
Hyperactivity of Adrenal cortex (Cushing’s
syndrome/disease)
Increased secretion of glucagon
Renal glycosuria
• Renal Tubular disease
____________
________________ disease
Fanconi’s Syndrome
Toxic renal tubular
Renal glycosuria
• Renal Tubular disease
•_____ Toxicity
• _______ Toxicity
• Inflammatory renal disease: ______,______
• Increased ____ without ________
•_______ renal glycosuria (Carrier protein def)
• Lowering of ————— (eg in ________)
Lead
Mercury
acute AGN, nephrosis
GFR; tubular damage
Hereditary
renal threshold ; pregnancy
Diabetes mellitus
Diabetes mellitus is a syndrome with disordered metabolism and inappropriate _______glycemia due to either a __________________ or ___________________
hyper
deficiency of insulin secretion or to a combination of insulin resistance and inadequate insulin secretion to compensate.
Diabetes mellitus
T1DM is due to ____________ predominantly by __________, and these patients are prone to _______
pancreatic islet B cell destruction
an autoimmune process
ketoacidosis
Diabetes mellitus
T2DM is the (more or less?) prevalent form and results from ________ with a defect in ____________
More
insulin resistance
compensatory insulin secretion
Dawn Phenomenon
The dawn phenomenon and the Somogyi effect cause (low or high?) blood sugar levels, especially in the ______________, in people who have ______.
High ; morning before breakfast
diabetes
Dawn Phenomenon
In the early morning hours, hormones (______,______,_______) cause the ____ to release (small or large?) amounts of sugar into the bloodstream.
growth hormone, cortisol, and catecholamines
liver
Large
Dawn Phenomenon
For most people, the body produces ____ to control the rise in blood sugar.
If the body doesn’t produce enough insulin, blood sugar levels can rise. This may cause (low or high?) blood sugar in the _________ ((before or after?) eating).
insulin
morning
Before
Somogyi Effect
If the blood sugar level _______ in the _____________,hormones(such as ______,_______, and _______ ) are released.
These help ______ the ____ blood sugar level but may lead to blood sugar levels that are (lower or higher?) than normal in the morning.
drops too low
early morning hours
GH, , cortisol, and catecholamines
reverse the low ; higher
Somogyi Effect
An example of the Somogyi effect is:
A person who takes________, doesn’t ________________, and the person’s blood ___________ during the night.
The person’s body responds to the low blood sugar by releasing hormones that raise the blood sugar level. This may cause a high blood sugar
level in the early morning.
insulin
eat a regular bedtime snack
sugar level drops
Somogyi Effect
If the blood sugar level drops too low in the early morning hours,hormones(such as GH, cortisol, and catecholamines) are released.
These help reverse the low blood sugar level but may lead to blood sugar levels that are higher than normal in the morning.
An example of the Somogyi effect is:
A person who takes insulin doesn’t eat a regular bedtime snack, and the person’s blood sugar level drops during the night.
The person’s body responds to the low blood sugar by releasing hormones that raise the blood sugar level. This may cause a high blood sugar
•
• •
level in the early morning.
