Diabete's Pharmagology Flashcards
Cells in the pancreas that synthesize and secrete glucagon
alpha cells
Cells in the pancreas that synthesize and secrete insulin
Beta cells
Location in the pancreas where endocrine function occurs
Islets of Langerhons
4 stimuli that trigger insulin release
- Cholinergic transmission
- Peptide hormones
- AAs
- glucose
The biggest stimuli of insulin release
Glucose
Transporter that uptakes glucose into beta cells of the pancreas
GLUT-2
GTPases that hep to target insulin-containing vesicles to a specific area of the membrane
Rab proteins
Proteins located on vesicles that bind calcium and promote docking to the membrane
SNAREs
GPCR on beta cell membrane that are activated by acetylcholine released by parasympathetic nerve endings
M3R
2 amino acids that can be taken up by beta cells and metabolized via TCA/Kerb’s cycle, increasing ATP
Alanine and glutamine
The 3 primary transcription factors for the insulin gene
- PDX-1
- MafA
- Beta2/NeuroD
Pathway induced by oxidative stress due to glucotoxicity and causes phosphorylation of key kinases, such as PI3K, deactivating them
JNK
Location of GLUT4 (Insulin-dependent)
Skeletal muscle and adipose tissue
Receptor that allows the brain to constantly take up glucose without needing insulin
GLUT1
The most important antigen in Type I DM
Insulin (B chain)
Acute metabolic complication in type I diabetes due to cells metabolizing triglycerides and AAs for energy
Ketoacidosis
The primary function of insulin in the vasculature
vasodilation
Glucose transporter located in the vascular endothelium
GLUT1
Cell adhesion molecules present in the endothelium that are important for the recruitment of macrophages and are decreased by PI3K/AKT pathways that are activated by insulin
ICAM-1 and VCAM-1
Important inflammatory cytokines present in insulin resistance that inhibit IRS1,2, eNOS and NO production
TNF-alpha and IL-6
MOA of sulfonylureas
Block ATP-sensitive K channels, stimulating insulin release from beta cells
3 1st generation sulfonylureas
tolbutamide
tolazamide
chlorpropamide
3 2nd generation sulfonylureas
glyburide
glipizide
glimpiride
Subunit of K channel that sulfonylureas bind to
SUR1 (sulfonylurea receptor 1), a regulatory subunit
2 meglitinides
repaglinide
nataglinide
Major elimination route of meglitinides
liver
MOA of metformin
inhibits mitochondrial respiratory complex-1, increasing AMP
MOA of thiazolidinedione
Activate PPARs, inducing transcription of genes involved in glucose metabolism
2 TZDs
rosiglitazone
pioglitazone
TZD withdrawn from market due to increased incidence of hepatitis
troglitazone
MOA of alpha-glucosidase inhibitors
Competitively inhibit digestion/absorption of carbs
2 alpha-glucosidase inhibitors
acarbose
miglitol
Peptide hormone that is co-secreted with insulin from pancreatic beta cells that slows gastric emptying, inhibits glucagon release and promotes satiety
Amylin
Amylin analogue used in conjunction with insulin in type I and type II DM
Pramlintide
Gut hormones that enhance insulin secretion in an insulin-dependent manner
Incretins
2 types of incretins
GIP
GLP-1
Protein that inactivates GLP-1 and GIP by cleaving N-terminal region
DPP4
2 DPP4-resistant GLP-1 analogues
exenatide
liraglutide
4 oral DPP4 inhibitors
sitagliptan
saxagliptan
linagliptan
alogliptan
Primary carbon source of fuel for all organisms
Glucose
2 main kinases that are involved in signal transduction regulated by glucose in pancreatic beta cells
ERK and PI3K/AKT
portion of proinsulin that is cleaved off to make insulin
chain C
Location of insulin receptor
ubiquitus
Type of receptor that insulin receptor is
tyrosine kinase
substrates that are recruited to the insulin receptor and activate PI3K
IRS1/2
Enzyme that inhibits glycogen synthase and is inactivated by insulin, allowing glycogen synthesis
GSK3
Pathways that is activated by insulin that activates protein synthesis
AKT/mTOR
Pathway that is involved in increased cell survival via inhibition of apoptosis by insulin action
PI3K/AKT
Pathway involved in the insulin-induced mitogenic responses (proliferation)
MAPK/ERK1,2
Primary function of insulin in the brain
satiety and appetite regulation
Primary function of insulin in the bone
stimulates bone formation and decreases osteoclast function
Cell surface molecules that bind peptide fragments from pathogens and are presented to thymocytes in the process of positive selection
MHC (major histocompatability complex)
Pathway that is responsible for increased proliferation and hypertrophy during hyperglycemia due decreased signaling through PI3K pathway
Ras/MAPK
Product of PI3K signaling that causes relaxation of the vasculature and is antithrombotic
NO
Potent vasoconstrictor and prothrombotic agent that is produced by RAS/MAPK signaling during hyperinsulinema
endothelin
Transporter that transports metformin into cells and is highly concentrated in hepatocytes
OCT1 (organic cation transporter-1)
3 affects of metformin in hepatocytes due to decreased AMP
- inhibits adenylate cyclase (alters gene expression)
- Inhibits FBPase (enzyme in gluconeogenesis)
- activates AMPK (inhibits lipid and cholesterol synthesis)
3 key genes involved in glucose metabolism that PPAR/RXR induces
IRS1,2, PI3K, GLUT4
2 mechanisms by which GLP-1 increases insulin secretion in beta-cells
- upregulates insulin gene transcription
2. increased Ca influx
