5070: DM

where do GLUT2 receptors work primarily?

liver

where do GLUT4 receptors primarily work?

adipose and muscle tissues

what type of GLUT receptor doesn’t need insulin to work?

GLUT 2

what is it called when the GLUT receptor moves itself after the insulin has bound to its receptor?

translocation

what are two molecular characteristics of glucose?

polar

hydrophilic

in what case is glucose transported against its [ ] gradient?

with SGLTs

in GI tract or renal tubules

what type of transport do SGLT utilize?

secondary active transport

how does secondary active transport work?

moves glucose against [ ] gradient with sodium

liver plays a crucial role in maintaining ______ homeostasis?

glucose

in a healthy person’s urine, we would expect to see zero of what?

glucose

during periods of _______ it is possible that we could detect glucose in the urine, why is this?

hyperglycemia

DM may overwhelm the # of transporters able to do SGLT

glycogen

storage form of glucose in the liver

glycogenesis

synthesis of glycogen

glycogenolysis

breakdown of glycogen

glycolysis

breakdown (metabolism) of glucose

gluconeogenesis

synthesis of new glucose, mainly by the liver

what is the dominant pancreatic hormone that is present when blood glucose is increased?

insulin

what does the liver do during a fed state? x 3 things

glucose uptake and glycogenesis

glycolysis (in excess, then makes acetyl CoA)

excess acetyl coA production in the liver during a fed state results in what?

triglycerides (via lipogenesis)

forms VLDLs

cholesterol

during a fed state, adipose tissue does what? x3

glucose uptake via GLUT4

fatty acid uptake (via lipoprotein lipase)

formation and storage of triglycerides

during a fed state, muscle tissue does what? x4

glucose uptake (GLUT4)

amino acid uptake (insulin facilitated)

some glycolysis for immediate energy use

protein and glycogen synthesis

how much of all the glycogen in the body is stored in muscle tissue?

¾

what enhances uptake of glucose?

physical activity

what does lipoprotein lipase do? what can the result of this first process do next?

breaks down triglycerides from VLDLs/chylomicrons to fatty acids

can diffuse into the adipocyte and re-form triglycerides w glycerol

where is lipoprotein lipase found?

on vascular endothelial cells, esp in adipose tissue

what does insulin promote with regard to lipoprotein lipase?

promotes its activity

insulin is the hormone that promotes the storage of this, via lipoprotein lipase molecules

fat storage

what are the two enzymes that uptake of fatty acids depends on ?

lipoprotein lipase

hormone-sensitive lipase

in what state does lipoprotein lipase work- fed or fasting?

fed

during what state does hormone sensitive lipase work- fed or fasting?

fasting

hormone sensitive lipase promotes what?

breakdown of stored triglycerides

allows the adipocyte to release free fatty acids and glycerol

catabolism is what?

energy release during fasting

what is catabolism stimulated by?

GLUCAGON and other hormones

what are the two liver pathways for producing glucose in a fasting state?

glycogenolysis

gluconeogenesis

what are the 2 catabolic pathways in muscle?

glycogenolysis

proteolysis

what does muscle release (x2) during catabolism, which are precursors that the liver uses in gluconeogenesis?

lactate

amino acids

during the proteolysis pathway of catabolism in muscle, what happens?

proteins broken down → release amino acids for liver gluconeogenesis

during glycogenolysis catabolic pathway in muscle, what happens?

breakdown of muscle glycogen produces G6P → converted to lactate → can travel through blood to liver for gluconeogenesis

during catabolism in adipose tissue, what is the process called?

lipolysis

what happens during lipolysis?

dec insulin, inc epi + cortisol, glucagon activates fat breakdown by hormone-sensitive lipase (HSL)

when the liver uses fatty acids for fuel, what is produced?

ketone bodies

liver ketogenesis is what?

when fatty acids are released by adipose lipolysis are oxidized by the liver at a high rate → produce acetyl CoA and ketone bodies

what 4 things cause the liver to do ketogenesis?

prolonged fasting

absence of insulin

very low carb diet

high glucagon and stress hormones

what might the use of ketone bodies create?

metabolic acidosis

what is insulin synthesized by and where?

in the pancrease by the B cells in the islets of Langerhans

what do B cells produce? what is it stored in in these cells?

proinsulin

stored in granules

in the granules of the B cell, what is proinsulin cleaved into

insulin and C-peptide

what cells produce glucagon?

a cells

what is the islet of langerhans made of?

cluster of pancreatic endocrine cells

what is proinsulin molecule made of? what is it joined by?

protein hormone with A and B chains,

joined by disulfide bonds

where is insulin molecule packaged?

secretory granules

what is the process that occurs to release insulin from proinsulin molecule?

what 2 molecules are the result of this?

connecting peptide is cleaved from proinsulin

C-peptide, insulin molecules

C-peptide is secreted with insulin in what ratio

one to one

in order to measure endogenous insulin production, what is the test that we can do?

if there is no insulin in the body, what will the result be?

C-peptide assay

no c-peptide

what are some characteristics that make C-peptide more reliable to measure than insulin?

more stable

longer circulation time

avoids first-pass metabolism in liver

what can the c-peptide assay test help us discern with regard to hypoglycemia?

differentiate different causes of it

what is the primary stimulus for insulin release

increased plasma glucose

how does glucose enter pancreatic B cells? what type is it not?

GLUT transporters (NOT GLUT 4)

presence of insulin triggers what?

cascade that results in exocytosis of vesicles containing insulin

upon ingestion of food, there is a brief rise in insulin release/secretion, what is this due to?

GIP and GLP-1 release from cells in the gut, which stimulates the secretion of insulin

what does GIP stand for?

glucose-dependent insulinotropic polypeptide

what does GLP-1 stand for?

glucagon-like peptide 1

what are also known as incretins?

what do they do?

GIP and GLP-1

stimulate the secretion of insulin

what inhibits glucagon secretion by alpha cells?

GLP-1

what are incretins broken down by?

DPP-4 enzyme

if there is a continuous presence of glucose, what does this cause with respect to insulin secretion?

longer phase of insulin secretion

when is more insulin secreted- orally or intraveous glucose exposure?

oral

what does glucose in the GI tract activate with anticipation of rising blood glucose following a meal?

feedforward mechanism

what do incretins enhance?

glucose-dependent insulin secretion

insulin in the liver enhances the uptake of what? why might this be a little different in the liver?

enhances glucose uptake

GLUT2 aren’t insulin-dependent

insulin in the liver increases storage and synthesis of what kind?

what does this ultimately cause?

glycogen storage and glycolysis

glycerol and fatty acids for triglyceride synthesis

what does insulin presence in liver inhibit?

gluconeogenesis and ketone production

insulin in the liver synthesizes and releases this in VLDLs

triglyceride

insulin presence in muscle increases the uptake, storage, and use of what?

glucose

insulin in the muscles increases uptake of this and synthesis of this other thing?

amino acids

protein

insulin in the fat/adipose tissue stimulates what other hormone?

what does insulin encourage that hormone to do?

lipoprotein lipase

triglyceride synthesis and storage

what does insulin presence in the fat/adipose tissues INHIBIT?

why is it a good idea to inhibit it?

hormone-sensitive lipase

this could cause lipolysis

insulin in the fat/adipose tissue increases the uptake and use of this substance:

glucose

insulin presence in the pancreas induces what specific action?

what does this do?

intraislet paracrine action

inhibits glucagon secretion

during the fasting state, what is the dominant hormone in the body- glucagon or insulin?

glucagon

what is responsible for most glucose production in a fasting state?

what time during the day is this production increased?

glucagon

early in the AM

where does glucagon come from (cell type and where from)?

alpha cells of pancreatic islets

what 3 things is glucagon inhibited by?

insulin (paracrine effect)

GLP-1

glucose at sufficient levels

what is the ‘counter-insulin’ hormone, and what does it tend to do?

glucagon

tend to increase blood glucose

what tissue does glucagon target primarily?

the liver

what are some general functions of glucagon in the body? x 4 things

increases glycogenolysis

increases gluconeogenesis

increases ketone body formation (ketogenesis)

decreases triglyceride synthesis

in the adipose tissue, what is glucagons ‘minor role’?

promotes lipolysis of triglycerides

what type of tissue doesn’t have glucagon receptors?

skeletal muscle

cortisol is considered another type of what hormone?

counter-insulin hormone

in the liver, what does cortisol do?

increases gluconeogenesis

in muscle, what does cortisol do?

increases proteolysis, increasing amino acid pool for glucose production

in adipose tissue, what does cortisol do?

what could this lead to?

when cortisol is high, it increases lipolysis

increased release of free fatty acids and glycerol, could increase ketone production

what is the overall effect of cortisol ?

to promote glucose production and release

epinephrine is also known as this type of hormone

counter-insulin

in the liver, epinephrine does what?

increases glycogenolysis, gluconeogenesis, ketogenesis, inhibits glycogenesis

in muscle, what does epinephrine do? x2 things

decreases glucose uptake

increases glycogenolysis which leads to glycolysis w release of lactate into the circulation

epinephrine in the adipose tissue does what? x 2 things

decreases triglyceride synthesis

increases lipolysis by activating hormone-sensitive lipase (could cause ketone production)

what is the overall effect of epinephrine in the body with regard to glucose/insulin?

to promote glucose production and release

what is the effects of counter-insulin hormones on patients in the hospital?

they have negative outcomes due to increased blood glucose levels

growth hormone is considered another type of what hormone?

counter-insulin hormone