Lec 3 - Insulin and Diabetes Basics Flashcards
Diagnosis of diabetes:
A1C greater than ____, or
fasting plasma glucose greater than _____,
or 2 hour plasma glucose tolerance greater than _____
6.5%;
126 mg/dL;
200 mg/dL
Type 1 DM:
autoimmune destruction of ___ cells, usually due to _____
presents in younger or older patients?
beta; viruses (in predisposed individuals);
younger
2 auto-antigens associated with type 1 DM:
insulin; glutamic acid decarboxylase
type 2 DM:
thin or obese patients?;
younger or older patients?
due to increased _____ to insulin
obese;
older;
resistance
hyperglycemia:
due to decreased glucose _____ in cells, increased _____, and increased _____
uptake; glycogenolysis;
gluconeogenesis
increased lipolysis can lead to ____;
glucagon levels are pathologically _____ in presence of increased blood glucose
ketoacidosis;
increased
neuropathy: increased blood glucose levels lead to increased utilization of the ____ pathway via ______; this causes increased _____ in neural cells
polyol, aldolase reductase;
water;
oxidation products of glucose react irreversible with proteins to form _____, which forms _____ _____ ____; theorized to be responsible for ____ complications
methylglyoxal, advanced glycation end-products;
long-term
aldolase reductase causes glucose to be converted into _____, which is converted into ____;
the hexosamine and PK C pathways are responsible for _____ modification
sorbitol, fructose;
protein
_____ is stimulated by NO and Ach and is thought to inhibit vasorelaxation, damaging cells
methylglyoxal
insulin receptor:
binding of the ___ subunit activates the catalytic activity of the ____ subunit. the beta segments contain the _____ ____ catalytic domains
alpha, beta, tyrosine kinase
tryosine kinase phosphorylation activates the:
_____ pathway, which stimulates cell growth and DNA synthesis;
_____ pathway, which stimulates glycogen, lipid, and protein synth. it also causes transportation of the _____transporter
RAS/MAP kinase pathway;
Phosphoinositide-3-kinase;
GLUT 4
insulin effects:
in peripheral tisusses, it stimulates ______ uptake. in skeletal muscle, ______ transport is increased. in adipose tissue, ____ storage is increased
glucose; amino acid;
TG
insulin in liver: glycogenolysis is \_\_\_\_\_\_; gluconeogenesis is \_\_\_\_; ketogenesis is \_\_\_\_\_; glycogen and TG synth is \_\_\_\_
inhibited, inhibited, inhibited;
stimulated
insulin release:
glucose enters ____ cells, causing an ____ in ATP; an increase in ATP (opens or closes) ____ channels.
beta, increase;
closes K+ channels
insulin release:
closure of ____ channels causes the cell to become more _____. this (opens or closes) ____ channels. (influx or efflux) of _____ occurs, causing insulin release
K, depolarized;
opens, Ca2+;
influx, calcium
glucagon is secreted during (fasting or fed) states, from ___ cells. it causes _____, ______, and _____
fasting, alpha;
glycogenolysis, gluconeogenesis, lipolysis
decreased serum FA ____ insulin action on ____ _____ and reduces hepatic glucose _____
increases, skeletal muscle;
production
glucose transporters: GLUT 1 is found \_\_\_\_\_; glut 2 is found in \_\_\_\_\_ and the \_\_\_\_\_ mainly; GLUT 3 is found in the \_\_\_\_; GLUT 4 is seen in \_\_\_\_ and \_\_\_\_;
which is induced by insulin?
which has the lowest Km?
widely expressed;
beta cells, liver (high Km);
neurons;
skeletal muscle, adipocytes;
GLUT 4;
GLUT 3
D cells produce ____. in addition to insulin, what other molecule do beta cells produce
somatostain; amylin
somatostatin does what?
amylin’s 2 main effects
decreases secretions;
slows gastric emptying, inhibits glucagon secretion
insulin is cleaved to A and B chains in _____ ____ by _____. _____ is also released
secretory granules; proconvertases;
C-peptide
GLP-1 peptide is released from ____ cells in the ____. it causes a _____ in insulin release, ____ glucagon, ____ gastric emptying. overall it causes a ____ in blood glucose
L, illeum;
increase, decreased, decreased;
decrease
which causes a larger increase in insulin, oral or IV glucose? what is this effect called? what do these do, in general?
oral; incretin effect; increase beta cell sensitivity
an oral glucose tolerance test with prolonged elevation of plasma glucose but normal or elevated insulin levels indicates what?
most common cause?
insulin resistance;
obesity
with insulin resistance, there is impaired glucose ____ in skeletal and adipose tissue; there is mobilization of ____ to other tissues;
acutely raising ____ levels causes insulin resistance
uptake (most important);
FA;
FA
insulin resistance can also be due to ____ in the insulin receptor;
for example, ____ phosphorylation inhibits signalling.
polymorphisms;
serine (rather than tyrosine)
insulin resistance due to mutated receptors is promoted by ____ uptake, ____ byproducts, and _____ mediators
FA, lipid; inflammatory (ie cytokines)
IL ___ from normal MQs increases insulin sensitivity. hypertrophied adipocytes cause release of ____, which attracts monocytes and causes infiltration of adipose tissue
10; MCP 1;
increased TNF alpha, IL6 –> insulin resistance
gestational diabetes:
normally, in early pregnancy there is _____ insulin sensitivity due to growth of ____;
in late pregnancy, there is _____ insulin sensitivity due to growth of ____
increased, placenta;
decreased, fetus
gestional diabetes is normally compensated by increased _____ secretion. if its not, it usually appears around 24 weeks, during the _____ ____ stage of gestation ____ the fetus has formed
insulin;
rapid growth;
after (ie doesn’t cause birth defects)
high levels of glucose in the fetus can cause ___somia, neonatal ____, and reduced synthesis of ____ due to increased fetal insuin
macro;
hypoglycemia;
surfactant –> neonatal respiratory distress
gestational diabetes, placental hormones:
_____ oppose insulin action. _____ contributes to insulin resistance
cortisol; placental lactogen (PL)
____ stimulates beta cell proliferation during pregnancy
prolactin
_____ are contraindicated during Gestational DM due to teratogenecity
glitazones
