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diabetes purohit
final
| Question | Answer |
|---|---|
| Diabetes mellitus:Recognized for centuries & characterized by | the excretion of sweet urine, polydipsia, polyuria, ketosis, coma & death. |
| Insulin exists as | preproinsulin, which is cleaved to proinsulin in the endoplasmic reticulum. |
| Proinsulin is a | large polypeptide consisting of an A & B chain & connecting peptide. |
| A- chain consists of | 21 amino acids & B-30 amino acids,Two chains are linked by two sulfide bonds. |
| Porcine & canine insulin molecules are | identical & similar to human,The difference is B-30 is alanine in porcine & canine, where as its threonine in human. |
| Feline & Bovine are | similar in structure. |
| The pancreatic hormones insulin & glucagon are important for | regulation of glucose, lipid & protein metabolism. |
| Although the pancreas secretes other hormones, such as | amylin, somatostin & pancreatic polypeptide, there function is not well established. |
| The islets of Langerhans:Beta cell secrete insulin & amylin, alpha cell secretes glucagon & delta cell secretes somatostatin, & PP cells present in the small number in the islets secretes | a hormone called pancreatic polypeptide. |
| There is a close interrelation among these cell in the islet of Langerhans allow cell-to-cell communication & | direct control of secretion of some hormones by the other hormone. |
| Insulin can inhibit glucagon secretion, amylin inhibits insulin secretion, & somatostatin | inhibits the secretion of insulin & glucagon. |
| Insulin has little effect on | uptake or use of glucose by brain. |
| Insulin secretion is not entirely controlled by | glucose. |
| Fat & protein, specially blood amino acids & other factors also | play important role in controlling insulin secretion. |
| Feed back relation between blood glucose & | insulin is an important factor. |
| Increase blood glucose causes | release of insulin. |
| Similarly decrease blood glucose causes | glucagon secretion, thus increases blood glucose levels. |
| Increase amino acids also | increases insulin secretion. |
| A mixture of several gastrointestinal hormones | gastrin, secretin, cholecystokinin & gastric inhibitory peptide- causes a moderate increase in insulin secretion. |
| Other hormones & autonomic nervous system affecting insulin & glucagon are | Growth hormone, cortisol, progesterone, estrogen, epinephrine, etc. |
| Autonomic System: Epinephrine & norepinephrine inhibit | insulin secretion whereas acetylcholine stimulates insulin secretion. |
| Glucagon | Effects the glucose metabolism. |
| Other effects of Glucagon are,Glucagon has | cardiovascular effects- increase blood pressure, cardiac out put, positive inotropic, etc. |
| Insuline Pharmacologic effects | Carbohydrate metabolism,Increases glycogen synthesis & decrease glycogenolysis,Fat Metabolism,Insulin increases lipid synthesis & decrease lipolysis,Protein metabolism,Insulin increases the uptake of amino acids & enhances protein synthesis,Potassium meta |
| Insulin is metabolized by | enzymes insulinase, insulin specific protease. |
| Insuline degradation occurs in | many tissues in the body. High activity has been found in liver, kidney, muscle, RBC etc. |
| The plasma half life is 5 to 10 minute, but the biological activity lasts | several hours. |
| Diabetes mellitus is usually seen | in adult animals, particularly in dogs & cats, age 7 years & older. |
| Diabetes is rare in | horse, cattle, & sheep. |
| Isolated cases have been reported in | mules, ferrets, pigs, newts, buffalos, monkey & fish,Also reported in several breeds of birds. |
| Type I diabetes is | insuline dependent or juvenile onset diabetes,That is insuline deficient diabetes. |
| Type II diabetes | thought to non-insulin dependent or maturity onset. |
| There can be relative or absolute insulin deficiency due to destruction of pancreatic islet tissue,or | In combination with any number of so called diabetogenic factors which interfere with normal insulin activity. |
| Various drugs or agents have been used to increase insuline secretion or its sensitivity in cases of | Type II diabetes. |
| Commercial insulin preparations are mostly of | human origin & produced using a recombinant DNA technique. |
| Only two preparations are marketed exclusively for animals are | Vetsulin & PZI Vet. |
| Crystalline zinc insulin (regular insulin) is a | short acting soluble human insulin,Can be given SC or IV, 4 to 5 times a day,Useful for rapid treatment for diabetic ketosis,The soluble insuline can also be of bovine or porcine insulin, dissolved in an aqueous solution. |
| Isophane insulin (NPH): Is an | intermediate-acting insulin that contains small amount of protamine, a basic protein that slows down the insulin absorption. |
| The onset of action for NPH insulin occurs | with in 2 hours, peak effect occurs in 8 -12 hours & action lasts 24 hours,Frequently used in dogs & cats for the glycemic regulation,Normally administered twice a day. |
| Serial blood glucose estimation or regular estimation of circulating glycated protein such as | fructosamine or glycosylated hemoglobin. |
| Lente insulin: Consist of | seven part ultralente insulin & three part of semilente insuline. |
| It is quite similar to | isophane insuline in its onset of action & duration of action. |
| Lente porcine (could be beef-pork mix) insuline (Vetsulin) is available for | animal use, particularly for dogs. |
| Vetsulin is | approved by FDA for use in animals. PZI insulin has recently been discontinued for use in animals. |
| Protamine zinc insulin | Lasts longer than isophane or lente insulin. |
| Protamine zinc insuline (PZI Vet) is | more commonly used for the treatment of diabetes mellitus in cats than dogs,Every 12 hours SC injection. |
| PZI Vet consists of | 90% bovine & 10% porcine insulin mix of protamine zinc insulin, for use in cats. |
| PZI insulin has been | recently discontinued. |
| Protamine zinc insulin of porcine or human origin is | used in dogs. |
| Given SC, action begins in | 4 hours, peak 16-18 hours, lasts up to 36 hours. |
| Insulin glargine (Lantus) | Is a recombinant human insulin analog with glycine residue at A-chain 21st amino acid residue & 2-arginine residues at B-chain 31st & 32nd amino acid residue. |
| It has been used for | both type 1 & type 2 diabetes mellitus , & there are decreased incidence of hypoglycemic episodes & improved control when compared with other intermediate acting insulin. |
| Has been used in both dogs & cats | insulin glargine. |
| Hypoglycemia,Results in insulin shock,characterized by | CNS disturbance, convulsion, coma,Treat with IV glucose. |
| Insulin resistance | Antibody formation,Stress may induce acute insulin resistance by increasing secretion of epinephrine & corticosteroids,Insulin receptor desensitization/ down-regulation could lead to insulin resistance. |
| Oral hypoglycemic agents have | variable success in treating canine & feline diabetes mellitus. |
| Sulfonylureas | Glipizide, glyburide,& glimepiride. |
| Biguanides | Metformin (1,1-dimethylbiguanide), also called Glucophase. |
| Thiazolidinediones,Among the thiazolidine compounds are | Troglitazone (Rezulin), Pioglitazone (Actos, Takeda), & Rosiglitazone (Av&ia). |
| Alpha- Glucosidase Inhibitors | Acarbose (Precose) & miglitol are complex oligosaccharides of microbial origin. |
| Sulfonylureas,Primary effect is | the direct stimulation of insuline secretion from betacell,Extrapancreatic effect includes increased peripheral insulin sensitivity & modification of hepatic gluconeogenesis & glycolysis,Only used if there is actual or potential insuline-secreting capacit |
| Used in type 2 diabetes,Have some success to treat diabetes in cats with | Glipizide, but other two glyburide & glimpiride, no information available for use in animals. |
| Over dose may cause | hypoglycemia, much milder than that induced by insulin. |
| Biguanides,Metformin It is an | oral antihyperglycemic, but not hypoglycemic drug. |
| Mechanism of action | Decreasing glucose output from liver, decrease glucose absorption from GI tract, increase insuline receptor sensitivity, metformin does not stimulate insuline secretion & thus does not cause hypoglycemia. |
| Therapeutic uses | Has been used in cats to treat diabetes, alone or in combination with sulfonylurea. |
| Thiazolidinediones,Are relatively new class of oral antidiabetic agents that includes | troglitazone,pioglitazone, rosiglitazone & darglitazone. |
| These drugs effect is mediated through the activation of | peroxisome proliferator activating receptor gamma ( PPAR-gamma) & retinoic X receptor, a subtype of the nuclear receptor superfamily of lig& activated transcription factors that is involved in the differentiation of adipose tissue. |
| They regulate the transcription of insulin responsive genes involved in the | control of glucose production, transport & utilization, thus improve insuline sensitivity. |
| Troglitazone pharmacokinetic in cat is similar to | human. |
| Darglitazone has also evaluated for | cat & does improve indices of insuline resistance,Not made available for veterinary use. |
| Acarbose (Precose) & Miglitol are | alpha glucosidase inhibitors, term applied to inhibitors of alpha amylase, sucrase, maltase & isomaltase which digests starch, & of brush border oligo- & disaccharide, which cleave off to glucose. |
| Thus these drugs inhibits the | conversion of complex carbohydrate & disaccharides to momosaccharides. |
| Acarbose has been used | in cats with diabetic control diet. |
| In diabetic dogs use of acarbose | less insulin is needed for control diabetes. |
| Insuline as a antiketogenic agent in | cattle. |
| Glucagon in use of | hypoglycemia. |
| Glucagon-like peptide 1 (GLP-1) is a | receptor agonist. |
| GLP-1 is an | incretin that augments insuline secretion after food intake,It also inhibits glucagon release & gastric emptying. |
| It is not a stable compound, there for a synthetic version of a peptide | exendin-4 (Extendine; Byett,), peptide isolated from the saliva of the gila monster, has been shown to bind & activate the known human GLP-1 receptor & is now used therapeutically for treatment of type- 2 diabetics. |
| A new class of drugs has also been developed in this area are | Sitagliptine (Januvia, Merck) & Vildagliptine (Galvus), have been approved for human use for type 2 diabetes. |