Lec 3 - Insulin and Diabetes Basics

Question 1

Diagnosis of diabetes:
A1C greater than ____, or
fasting plasma glucose greater than _____,
or 2 hour plasma glucose tolerance greater than _____

Answer 1

6.5%;
126 mg/dL;
200 mg/dL

Question 2

Type 1 DM:
autoimmune destruction of ___ cells, usually due to _____
presents in younger or older patients?

Answer 2

beta; viruses (in predisposed individuals);

younger

Question 3

2 auto-antigens associated with type 1 DM:

Answer 3

insulin; glutamic acid decarboxylase

Question 4

type 2 DM:
thin or obese patients?;
younger or older patients?
due to increased _____ to insulin

Answer 4

obese;
older;
resistance

Question 5

hyperglycemia:

due to decreased glucose _____ in cells, increased _____, and increased _____

Answer 5

uptake; glycogenolysis;

gluconeogenesis

Question 6

increased lipolysis can lead to ____;

glucagon levels are pathologically _____ in presence of increased blood glucose

Answer 6

ketoacidosis;

increased

Question 7

neuropathy: increased blood glucose levels lead to increased utilization of the ____ pathway via ______; this causes increased _____ in neural cells

Answer 7

polyol, aldolase reductase;

water;

Question 8

oxidation products of glucose react irreversible with proteins to form _____, which forms _____ _____ ____; theorized to be responsible for ____ complications

Answer 8

methylglyoxal, advanced glycation end-products;

long-term

Question 9

aldolase reductase causes glucose to be converted into _____, which is converted into ____;

the hexosamine and PK C pathways are responsible for _____ modification

Answer 9

sorbitol, fructose;

protein

Question 10

_____ is stimulated by NO and Ach and is thought to inhibit vasorelaxation, damaging cells

Answer 10

methylglyoxal

Question 11

insulin receptor:
binding of the ___ subunit activates the catalytic activity of the ____ subunit. the beta segments contain the _____ ____ catalytic domains

Answer 11

alpha, beta, tyrosine kinase

Question 12

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

Answer 12

RAS/MAP kinase pathway;

Phosphoinositide-3-kinase;

GLUT 4

Question 13

insulin effects:
in peripheral tisusses, it stimulates ______ uptake. in skeletal muscle, ______ transport is increased. in adipose tissue, ____ storage is increased

Answer 13

glucose; amino acid;

TG

Question 14

insulin in liver:
glycogenolysis is \_\_\_\_\_\_; 
gluconeogenesis is \_\_\_\_;
ketogenesis is \_\_\_\_\_;
glycogen and TG synth is \_\_\_\_

Answer 14

inhibited, inhibited, inhibited;

stimulated

Question 15

insulin release:

glucose enters ____ cells, causing an ____ in ATP; an increase in ATP (opens or closes) ____ channels.

Answer 15

beta, increase;

closes K+ channels

Question 16

insulin release:
closure of ____ channels causes the cell to become more _____. this (opens or closes) ____ channels. (influx or efflux) of _____ occurs, causing insulin release

Answer 16

K, depolarized;
opens, Ca2+;
influx, calcium

Question 17

glucagon is secreted during (fasting or fed) states, from ___ cells. it causes _____, ______, and _____

Answer 17

fasting, alpha;

glycogenolysis, gluconeogenesis, lipolysis

Question 18

decreased serum FA ____ insulin action on ____ _____ and reduces hepatic glucose _____

Answer 18

increases, skeletal muscle;

production

Question 19

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?

Answer 19

widely expressed;
beta cells, liver (high Km);
neurons;
skeletal muscle, adipocytes;

GLUT 4;
GLUT 3

Question 20

D cells produce ____. in addition to insulin, what other molecule do beta cells produce

Answer 20

somatostain; amylin

Question 21

somatostatin does what?

amylin’s 2 main effects

Answer 21

decreases secretions;

slows gastric emptying, inhibits glucagon secretion

Question 22

insulin is cleaved to A and B chains in _____ ____ by _____. _____ is also released

Answer 22

secretory granules; proconvertases;

C-peptide

Question 23

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

Answer 23

L, illeum;
increase, decreased, decreased;
decrease

Question 24

which causes a larger increase in insulin, oral or IV glucose? what is this effect called? what do these do, in general?

Answer 24

oral; incretin effect; increase beta cell sensitivity

Question 25

an oral glucose tolerance test with prolonged elevation of plasma glucose but normal or elevated insulin levels indicates what? most common cause?

Answer 25

insulin resistance; obesity

Question 26

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

Answer 26

uptake (most important); FA; FA

Question 27

insulin resistance can also be due to ____ in the insulin receptor; for example, ____ phosphorylation inhibits signalling.

Answer 27

polymorphisms; | serine (rather than tyrosine)

Question 28

insulin resistance due to mutated receptors is promoted by ____ uptake, ____ byproducts, and _____ mediators

Answer 28

FA, lipid; inflammatory (ie cytokines)

Question 29

IL ___ from normal MQs increases insulin sensitivity. hypertrophied adipocytes cause release of ____, which attracts monocytes and causes infiltration of adipose tissue

Answer 29

10; MCP 1; increased TNF alpha, IL6 --> insulin resistance

Question 30

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 ____

Answer 30

increased, placenta; | decreased, fetus

Question 31

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

Answer 31

insulin; rapid growth; after (ie doesn't cause birth defects)

Question 32

high levels of glucose in the fetus can cause ___somia, neonatal ____, and reduced synthesis of ____ due to increased fetal insuin

Answer 32

macro; hypoglycemia; surfactant --> neonatal respiratory distress

Question 33

gestational diabetes, placental hormones: | _____ oppose insulin action. _____ contributes to insulin resistance

Answer 33

``` cortisol; placental lactogen (PL) ```

Question 34

____ stimulates beta cell proliferation during pregnancy

Answer 34

prolactin

Question 35

_____ are contraindicated during Gestational DM due to teratogenecity

Answer 35

glitazones