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139 Cards in this Set
- Front
- Back
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what is diabetes
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abnormal glucose metabolism pancreas disorder insulin resistance autoimmune metabolic disorder B-cell dysfunction genetic |
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cells that secrete glucagon
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alpha
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cells that secrete insulin
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beta
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secrete somatostatin (GHIP)
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Delta
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stimulates insulin gene expression in beta cells
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glucose transporter
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glucose is produced in
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alpha cells
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used as an indicator of new insulin expression
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C protein
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the insulin receptor is a
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RTK
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what activates the insulin receptor
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insulin or insulin like growth factor
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insulin binding and transduction mobilizes _______ transporter to the surface
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Glut
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IGF effect is more/less metabolic than insulin
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less
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insulin is the major _________ regulator of dietary glucose disposition
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anabolic
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insulin directs metabolism of
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FA's and AA's
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Glucogon stimulates
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catabolic glycogen and FA's to make glucose
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insulin is located in the adrenal gland
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pancreatic islet cells
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insulin secretion is regulated by
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glucose levels
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insulin release is mediated by a ________ receptor
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RTK
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Insulin causes increased _____ of glucose and activates _________
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uptake, glycogen synthetase
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glucagon acts via
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GPCR
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Insulin sensitizers include
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thiazolidinediones, biguanides
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thiazolidinediones act by
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binding PPAR's
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Thiazolidinediones
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Pioglitazone Troglitazone Rosiglitizone |
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alpha-glucosidase inhibitors act via
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stopping digestion of sugars
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alpha-glucosidase inhibitors
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glyset precose aracabose |
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Secretagogues act by
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stimulating insulin secretion by blocking K+ channels
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Secretagogues include
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sulfonylureas and meglitinides
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sulfonylureas
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amaryl diabeta diabinese dymelor glucotrol |
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Meglitinides |
prandin |
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Insulins used in diabetes include
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fast: lispro, aspart, glulisine long: glargine, detemir inhalable: exubera |
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The prototypical glucocorticoid
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cortisol (also cortisone)
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prototypical mineralcorticoid
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aldosterone |
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Corticosteroid hormones
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cortisol, hydrocortisone, glucocorticoid, aldosterone, androgen, dehydroepiandrosterone |
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rapid acting insulin
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lispro
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short acting insulin
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novolin
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intermediate insulin
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NPH insulin
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long acting insulin
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insulin detemir
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Metformin activates ________ to lower glucose w/out producing hypoglycemia
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AMPK
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Euglycemic
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lowers glucose w/out producing hypoglycemia
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first generation sulfonylurea
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tolbuamide
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second generation sulfonylurea
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glipizide, glyburide less side effects |
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K(ATP) modulators
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Repaglinide, Neteglinide
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sulfonylureas act by
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increasing insulin release in pancreas by K+ efflux inhibition and Beta cell depolarization
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Meglitinides act by
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closing K+ channels (K(ATP) modulators) rapid acting, short duration |
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starlix is a _______ with lower potential for ________-
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meglitinide (K+ inhibitor), hypoglycemia
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Adrenocorticotropic hormone is released by |
the anterior pituitary by corticotropin-releaseing hormone binding
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PPAR
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peroxisome proliferator activated receptor
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Thiazolidinediones which bind PPAR's act by
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decreasing insulin resistance in adipocytes risk of edema, HF, osteoporosis |
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Other insulin drugs include:
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Alpha glucosidase inhibitor (Acarbose) GLP receptor agonists (exenatide) |
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GLP-1 agonists
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exenatide, liraglutide, dulaglutide increase glucose-dependent insulin secretion |
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Corticosteroids are
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75% protein bound metabolized by conjugation in liver with short half-lives |
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dogs are
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type I diabetic
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cats are
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type II diabetic
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cats and dogs usually need
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two daily doses of insulin
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oral agent of diabetic cats
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glipizide, levemir, lantus
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DPP-4 inhibitors
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sitagliptin, saxagliptin, linagliptin increase glucose dependent insulin secretion |
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Glucocorticoids stimulate
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gluconeogenesis and glycogen synthesis in liver catabolic outside of liver increased insulin secreation decreased peripheral glucose uptake fat deposition availability of glucose to brain |
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oral agent of diabetic dogs
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NPH, Lente
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glucocorticoids are also
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anti-inflam decrease capillary permeability increase platelets and RBC's increase gastric secretions excitatory in nervous system |
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Corticosteroids act on
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nuclear receptors (GRE, Hsp90example)
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Synthetic corticosteroids
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prednisone methylprednisolone triamcinolone betamethasone dexamethasone |
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Glucocorticoid antagonist
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metyrapone ketoconazole aminoglutethimide mifepristone |
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glucocorticoid toxicity
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muscle wasting fat deposition skin thinning/bruising hyperglycemia diabetes osteoporosis ulcers |
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Glucocorticoid therapy
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addison's pulmonary conditions rheumatism/inflammatory disorders immune suppression |
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Mineralocorticoid effects
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aldosterone increases urinary reabsorption of Na+ and in other tissues decreases K+ and H+ reabsorption acts by a nuclear receptor |
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Mineralocorticoid toxicity
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hypernatremia hypokalemia alkalosis excess plasma hypertension |
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mineralocorticoid agonists
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deoxycorticosterone fludrocortisone |
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mineralocorticoid antagonists
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spironolactone eplerenone drospirenone |
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cats are less sensitive to corticosteroids SE's and take
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prednisolone
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dogs take
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fludrocortisone
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Non-steroid receptors
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insulin (RTK) cytokine GPCR's |
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Crystal structures of GPCR's are only bound to
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antagonists
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RTK have alpha and beta which bind to
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alpha: hormone beta: ATP and TK |
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Insulin receptor activates
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IRS-1 regulates glut-4 phosphorylation control of glycogen synthetase |
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JAK-STAT Pathway
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recruits kinase activity for cytokine R's
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Steroid recptors
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nuclear receptor superfamilies lipophilic permeate through membrane and bind in cytoplasm or nucleus regulated nuclear transcription |
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nuclear receptor function
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1: bind in cyto or nucleus 2: ligand-receptor migrate to nucleus 3: L-R binds to DNA, regulates transcription 4: 5-6 domains A-F (E is ligand binding), hydrophobic binding pocket, zinc fingers 5: PPAR"S |
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Steroid hormones have
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nuclear and non-nuclear mediated effects (shorter time scales, regulation of enzymes and ion channels)
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ovary secretes Progesterone in response to LH which
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inhibits release of GnRH from hypothalamus and inhibits LH release
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Pituitary hormones include
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growth hormone prolactine oxytocin vasopressin TSH, ACTH, FSH, LH |
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posterior pituitary releases
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oxytocin and ADH
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GHRH is secreted from
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arcuate nucleus of the hypothalamus
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growth hormone (somatotropin) is released form the _____ pituitary and is similar to ________
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anterior, prolactin
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Growth hormones actions are
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growth stimulation IGF synth/cartilage synth |
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prolactin is released from
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anterior pituitary
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inhibits prolactin
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dopamine, bromocriptine, pergolide
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prolactin stimulates
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lactation
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Oxytocin is release from and lasts
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posterior pituitary 5 min half life
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oxytocin stimulates
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contraction, lactation
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stops oxytocin effects
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beta agonists
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ADH (vasopressin) is released from and by and lasts
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posterior pituitary 20 min half life increased tonicity or low BP stimulate vasopressin release |
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ADH has V2>V1 and activates
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kidney reabsorption of water
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ACTH is released from by
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anterior pituitary, corticotropin-releasing hormone
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CRH
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inhibit food uptake
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ACTH action
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agonist on Gs increases steroid synth produces gluco and mineralocorticoids and androgens |
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ACTH synthetic
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cosyntropin
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Thyroid stimulating hormone is released by
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released in AP in response to TRH TRH is regulated by thyroxine |
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TSH acts by |
Gs to increase iodine uptake and thyroid hormone production
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FSH is released from and by
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AP in response to GnRH synthetic GnRH is leuprolide |
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FSH acts via and to
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Gs, stimulates gametogenesis and gollicular enlargement (ovulation) necessary for steroidogenesis |
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LH is released by and from
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AP regulated by GnRH
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LH stimulates
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gonadal steroid production follicular development/ovulation (progesterone, androgen) |
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Orexin stimulates
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appetite, wakefulness
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female gonadal system
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location: ovaries synth: similar to corticosteroids estrogens: estradiol, progesterone |
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Male gonadal system
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location: testes synth: adrenals Androgens: testosterone |
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regulation of sex steroids is via
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GnRh, FSH, LH
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Sex steroids are highly
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lipid (good oral agents) high plasma protein binding |
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synthetic estrogens include
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ethinyl estradiol mestranol diethylstilbesterol chlortrianisene |
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estrogen actions
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female reproductive system development anabolic blood coagulation edema smooth muscle and sympathetic nervous |
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synthetic progestins
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norethindrone ethynodiol norgestrel desogestrel |
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progestin actions
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little anabolic effect inhibits ovulation negative feedback of hypothalamic and pituitary |
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too much sex steroids for females
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vaginal bleed migrains cancer thromboembolism serum lipids high liver issues |
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sex steroid antag
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tamoxifen (SERM) toremifine (SERM) clomifene (Anti-estrogen) fulvestrants (Anti-estrogen) mifepristone (anti-progestin) |
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female sex steroids are given for
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post menapaus diagnosis contraception cancer replacement |
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contraceptives |
inhibit ovulation (central) alter ovarian, tubular, and uterine funciton (peripheral) |
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combination sex steroids have
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ethinyl estradiol levonorgestrel (progestin) |
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Progestins
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norethindrone norgestrel |
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Androgens act by
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feedback inhibition of hypothalamic and pituitary factos develop male reporduction increase libido anabolic |
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too much male sex steroids
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muscle liver issues cancer edema CNS development issues inhibit hypothalamic-pituitary-reproductive axis |
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Male sex steroids are given as
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replacement therapy anemia osteroporosis growth stimulants muscle builders |
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Androgen antag
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flutamide (prostate cancer) spironolactone (competes with dihydrotestosterone) lower testosterone levels |
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thyroid is one of the |
largest endocrine glands found beneath larynx and wraps trachea |
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Thyroid hormones
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T3 is more active than T4 T4 is deiodinated to T3 in periphery (beta blockers inhibit this) |
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Thyroid hormones are regulated by
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hypothalamic TRH and pituiarty TSH iodine metabolism |
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TSH is released from and in response to
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anterior pituitary in response to TRH
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TH disposition
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good oral agent bound to plasma T4 to T3 by liver microsomes |
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Thyroglobulin
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used and produced in thyroid
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TH actions
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catabolism (ATP turnover, O2 use increase) tissue development increase protein xynth |
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TH receptors are
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nuclear (alpha or beta with 1 or 2 subtype)
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TH toxicity
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heat intolerance weight loss nervousness HR increase bone growth |
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Anti-TH
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thioamides (methimazole): inhibit iodine organification anions (pertechnetate TcO4-) iodides iodinated contrast media |
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TH applications
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hypothyroidism (give T4) Hyperthyroidism/graves disease (give methimazole, propylthiouracil (antithyroids)) |
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Calcitonin is from and causes
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from thyroid causes decrease in plasma calcium and increase in bone calcium PTH and calcitonin are ying-yang |
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PTH is released from and regulates
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parathyroid (behind thyroid) regulates calcium levels calcium regulates PTH secretion |
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PTH comes from
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pro-PTH
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PTH causes
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increase serum calcium and decrease in phosphate acts via GPCR |
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PTH receptors
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PTH 1: bone and kidney PTH 2: CNS, pancreas, placenta Gs |
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PTH applications
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osteoporosis consider: vitamin D: Calcipotriol and Calcitonin |
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bone density increase
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estrogens androgens calcitonin GH |
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bone density decrease
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glucocorticoids
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