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diabetes purohit


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.
Created by: alljacks



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