Cell Signaling II/Diabetes Flashcards
what are the types of diabetes
- Type 1: Insulin dependent/juvenile- autoimmune destruction of pancreatic beta cells results in lack of insulin production
- Type 2: Non insulin dependent DM or adult onset diabetes- insulin resistance due to insuling signaling defect.
- Gestational: happens during pregnancy
What are the stats of diabetes
- 25.8 million americans (8.3%) have it.
- 18.8 million diagnosed - 0.2 million under 20 yrs old
- 5-10% of diabetics are Type 1
- 4% of pregnant women develop gestational diabetes.
Currently, 1 in ____adults have diabetes
10; but if trends continue; 1 in 3 adults could have diabetes
What are symptoms of acute onset diabetes
- Polyuria: excess glucose, urea and ketone bodies getting excreted by kidneys + water goes with them.
- Polydypsia: Dehydration leads to excess thirst. This can lead to xerostomia and dental caries.
- Polyphagia: lack of insulin action on anorexigenic peptide synthesis leads to excessive hunger.
In a normal situation, we’re mobilizing fuel. Insulin activates GLUT 4 transporter to uptake glucose to allow nutrients to be stored. In diabetes we lose affect of insulin. Locked in a ____type of metabolism
glucagon.
Can bypass insulin by :
excercise
excess acetyl CoA goes to:
ketone bodies
what is diabetic ketoacidosis
caused by insufficient insulin leading to persistenly high blood glucose (>300mg%)
what is DKA associated with
- infection -40%
- missed insulin - 25%
- untreated/misdiagnosed diabetes - 15%
- Other stressors like heart attack or stroke
what are DKA symptoms
- Acetone breath
- high blood glucose
- thirst
- urination
- weakness
- confusion
- vomiting
- abdominal pain
- shortness of breath/ inc respiration
what are diagnostic tests
- Fasting plasma glucose test (FPG) - prick your finger. Should be below 100
- 100-125mg% = pre diabetes
- >126 mg% diagnostic - Oral glucose tolerance (OGTT) - BG levels monitored over 2-3 hr period
- 140-199 mg% = pre diabetes
- >200 mg% diagnostic - Hemoglobin A1c - glycosylated Hb.
- <7% management goal - C- peptide - verifies if Type 1 or Type 2 diabetic
what is the glucose tolerance test
measures blood glucose levels. Never should be above 135-140/150. Diabetics usually above 200. Gray area = pre diabetes.
How does C peptide test work
related to idea that insulin is processed into its two chains held together by disulfide bonds and C peptide. Should have equal amounts of insulin and C peptide. If the only insulin you have is artificial insulin, then it doesnt have any C-peptide associated with it, so c peptide levels will be very low, so True Type 1.
What is the treatment goal?
lower blood glucose!
you can enhance insulin secretion and enhance blood glucose uptake and bypass insulin signaling by excercise and inc in AMP kinase and adiponectin with some drugs
How does AMP kinase get activated and what does it do
PPAR gamma - a transcription factor that activates adiponectin which activates AMP kinase which activates GLUT4 transporters which increases muscle FA uptake and decreases liver gluconeogenesis. Ehances insulin sensitivity
What are treatment options for diabetics
- weight loss: target adipose; effect is that it restores insulin
- excercise: targets muscle, AMPK activation and enhances glucose uptake
- metformin: AMPK activator. Enhances glucose uptake
Why are K+ channel blockers being used for insulin secretion
K+ channels go out and ATP K+ channel closes whenever ATP levels increase when glucose is available. ATP binds to K+ channel and closes it. WHen it closes you get a depolarization affect and calcium channel opens which is a big signal for excytosis of vesicles. Excytose insulin packed vesicles.
what activates PPARgamma
Thiazolidinediones which activate adiponectin which activate AMPK
What happens if you have long term diabetes
increased risk for:
- cardiovascular disease & stroke
- end stage renal disease
- peripheral neuropathy
- diabetic retinopathy: major cause of blindness
- prolonged wound healing
- infection
- periodontal disease: loss of attachment, get deep pockets breaking down periodontal ligament and bone around teeth.
What causes long term sequalae?
glucose spontaneously participates in a schiff reaction with free amino groups within proteins which results in ketoamine linkage of glucose to amino termini and lysine residues of proteins, a process called GLYCATION. The products are called advanced glycation end products (AGEs)
What are RAGEs
Pattern recognition receptor (like Toll receptor which activate NFkB and AP- 1 which act inflammatory response) RAGE receptors do the same thing! Set up chronic inflammation. Glycated products bind with rage receptors and activate NFkb and the inflammatory response.
What does chronic vascular inflammation lead to
- Impaired vasodilatation (high BP)
- impaired flow mediation dilation
- impaired response to adenosine
- inc stiffness of aorta
- renal and carotid artery stenosis (kidney damage and stroke)
what is diagnosis of periodontitis
- appearance of gingivae- redness and swelling
- bleeding on probing
- pocket probing depth
- tooth mobility
- alveolar bone loss
what happens during periodontal disease
toll receptors being activated bc bacteria are in the pockets. You get NFkB and prostanoids and cytokines. CAL increases as well as tooth mobility and loss
