Veterinary Pharmacology of Hormone secreted by pancreas

“HORMONES
SECRETED BY
PANCREAS”
P R E S E N T E R : S A B A L P O K H A R E L

PANCREAS
The pancreas is an organ of the digestive system and endocrine system. It is located in
the abdomen behind the stomach and functions as a gland.
The pancreas has both an endocrine and a digestive exocrine function.
The endocrine part of pancreas is made up of small bundles of cells called as Islet of
Langerhans.

PANCREAS
There are five main types of endocrine cells in Pancreas as follows.
Alpha cells = secretes Glucagon
Beta cells = secretes Insulin
Delta cells = secretes Somatostatin
Gamma cells = secretes Pancreatic Polypeptide (PP)
Epsilon cells = secretes Ghrelin

GLUCAGON
Glucagon is a hormone that raises blood glucose levels by stimulating the liver to
convert its glycogen into glucose.
It is secreted by alpha cells of Islet of Langerhans.
Alpha cells make up to 15-20% of total Islet cells.

PHARMACOLOGICAL ACTION
Glucagon’s main pharmacologic activities are to increase blood glucose and relax
smooth muscle of the GI tract. The mechanisms of action for its GI effects are poorly
understood.
Glucagon causes Lipolysis and Ketogenesis.
Glucagon enhances Gluconeogenesis and urea formation.
It primarily increases blood glucose by stimulating hepatic glycogenolysis.
Glucagon increases alanine uptake by liver and hepatic glucose output.

Glucagon stimulates insulin secretion and hepatic ketone body formation in presence
of low insulin levels.
Glucagon secretion is stimulated by Low levels of blood glucose (hypoglycemia),
Norepinephrine, Arginine, Cholecystokinin (CCK), Gastrin, Glucocorticoids etc.
Glucagon secretion is inhibited by High blood glucose, Somatostatin, GABA, Fatty
acids.

PHARMACOKINETICS
Glucagon must be administered parenterally as it is destroyed in the gut after oral
dosing.
After intravenous injection, maximum glucose levels are attained within 30 minutes;
hyperglycemic effects persist up to 90 minutes after dosing.
Glucagon is degraded in the plasma, liver and kidneys; in humans, plasma half-life is
around 10 minutes.

USES/INDICATION
In small animals, glucagon is used to increase blood glucose in patients with excessive
insulin levels (Insulinomas).
In Dairy cows, glucagon is used in the treatment of fatty liver syndrome.
In human medicine, glucagon is used in treating the cardiac manifestations of beta-
blocker and calcium-channel blocker overdoses.

DRUG INTERACTIONS
Anticoagulants: Their effect is increased when glucagon is simultaneously administered

ADVERSE EFFECTS
Adverse Effects of Glucagon is very rare.
Nausea and vomiting can be observed after administration.
Hypokalemia and Hypersensitivity reactions.

DOSAGE
Dogs and Cats
For hypoglycemic treatment
1 mg of glucagon is reconstituted per manufacturer directions and then added to
mL of 0.9% Sodium Chloride.
Initially give a 50 ng/kg bolus IV and then administer at 5-15 ng/kg/min. (ng=
nanogram)
Cattle
For treatment of fatty liver in dairy cows
5 mg glucagon in 60 mL of normal saline SC, every 8 hours (15 mg/day) for 14 days

INSULIN
Insulin is a pancreatic hormone secreted by beta cells of islet of Langerhans that is
used to treat diabetic ketoacidosis, uncomplicated diabetes mellitus and as adjunctive
therapy in treating hyperkalemia.
Aside of Insulin, the other secretions of Beta cells are:
Proinsulin
C peptide
Islet amyloid polypeptide (IAPP or amylin): Slows gastric empyting and prevents spikes
in blood glucose level
Gamma- aminobutyric acid (GABA)

STRUCTURE OF INSULIN
Insulin is composed of two peptide chains referred to as the A chain and B chain.
A and B chains are linked together by two disulfide bonds, and an additional disulfide
is formed within the A chain.
The A chain consists of 21 amino acids and the B chain of 30 amino acids as shown in
figure below.

Insulin facilitates uptake and entry of glucose in the muscles, adipose and several other
tissues.
Insulin stimulates the liver to store the glucose in form of glycogen.
Insulin promotes synthesis of fatty acid in liver.
Insulin Inhibits breakdown of fat in adipose tissue.
The hormone stimulates lipogenesis, increases protein synthesis, and inhibits lipolysis
and free fatty acid release from adipose tissues.
Insulin promotes an intracellular shift of potassium and magnesium.

ANTI-DIABETIC ACTION OF INSULIN

USES/INDICATIONS
Insulin preparations have been used for the treatment of diabetic ketoacidosis,
uncomplicated diabetes mellitus, and as adjunctive therapy in treating hyperkalemia.

PHARMACOKINETICS
Insulin is metabolized mainly by the liver and kidneys and also muscle and fat to a
lesser degree.
It is metabolized by enzymatic reduction to form peptides and amino acids.
Insulin is filtered by the renal glomeruli and is reabsorbed by the tubules, which also
degrade it.
The half-life of insulin is less than ten minutes.

PRECAUTIONS AND ADVERSE EFFECTS
Precautions
Do not inject insulin at the same site day after day or lipodystrophic reactions can
occur.
There is not much contraindication for insulin.
Adverse Effects
Hypoglycemia
Insulin-induced hyperglycemia i.e. Somogyi effect
Local reactions to the foreign proteins.

DOSES
Dogs and Cats
For treatment of diabetic ketoacidosis use regular insulin Initial Dose: 0.2 U/kg IM into
muscles of the rear legs; repeat IM doses of 0.1 U/kg hourly.
For treatment of severe hyperkalemia give regular insulin 0.25–0.5 U/kg slow IV bolus
followed by 50% dextrose solution.
Cattle
For treatment of ketosis give PZI insulin 200 Units (total dose) SC once every 48

DIABETES MELLITUS
Diabetes mellitus is a chronic, metabolic disease characterized by elevated levels of
blood glucose, which leads over time to serious damage to the heart, blood vessels,
eyes, kidneys and nerves.
Most symptoms secondary to hyperglycemia are polyuria, polydipsia and polyphagia.

CLASSIFICATION OF DM
Insulin Dependent Diabetes Mellitus (IDDM) or Type 1 DM
Non-Insulin Dependent Diabetes mellitus (NIDDM) or Type 2 DM
Gestational Diabetes mellitus
Malnutrition related DM (MRDM)
Other types

IDDM OR TYPE 1 DM
It results from the failure of pancreas to produce enough insulin or it is insulin
dependent DM.
It is also known as Juvenile Diabetes since age of onset is juvenile.
Ketonuria is common but the body weight remains normal.
For treatment of IDDM, Insulin is necessary.

NIDDM OR TYPE 2 DM
It begins with insulin resistance, a condition in which cell fails to respond to insulin
properly.
It is also adult onset diabetes since adult are mostly affected.
Mostly body is obese and there is no ketonuria.
Treatment with Insulin is usually not required.

GESTATIONAL DM
It mostly occurs in pregnant women without the previous history of diabetes.

HYPOGLYCEMIC DRUGS / ANTI DIABETIC
DRUGS
A) Injectable Hypoglycemic Drugs i.e. Insulin
B) Oral hypoglycemic drugs
1) Sulfonylureas
(a) First generation: Tolbutamine, Chlorpropamide, Tolazamide, Acetohexamide
(b) Second generation : Glibenclamide, Glipizide
 Acts indirectly
 They stimulate β-cells and release insulin
 30 % of β-cells most be active for their action.
 Should not be used in pregnancy because they are teratogenic.
 Mainly used in NIDDM.

DRUGS
2) Biguanides: Metformin, Phenphormin, and Buformin
Acts directly by increasing insulin sensitivity.
Generally metformin is the first medication prescribed for Type 2 DM (NIDDM).
It has No effects on β-cells.
Effective in IDDM also.
Lactic acidosis is harmful side effect.

DRUGS
Metformin
Oral anti-hyperglycemic agent that is useful in the treatment of non-insulin
diabetes mellitus (NIDDM) in cats.
It is contraindicated in patients hypersensitive to it, with renal dysfunction, metabolic
acidosis, or temporarily when iodinated contrast agents are to be used.
Adverse effects may include lethargy, anorexia, vomiting, & weight loss

DRUGS
3) Meglitinides
Meglitinides modulate β-cell insulin release.
Meglitinides are oral medications used to treat type 2 diabetes.
They work by triggering production of insulin.
4) Thiazolidinediones: Decreases Insulin resistance
5) Alfa-glycosidase inhibitors: delay CHO absorption

SOMATOSTATIN
Somatostatin is a polypeptide made up of 41 amino acids.
Somatostatin also known as growth hormone-inhibiting hormone (GHIH) is produced
by delta cells of Islet of Langerhans and hypothalamus.
Somatostatin is a polypeptide made up of 41 amino acids.
It inhibits Insulin and Glucagon secretion and also functions as neurotransmitter in
Brain
Somatostatin is secreted in response to high level of other endocrine hormones.
Somatostatin secretion is inhibited by low levels of other endocrine hormones.

SOMATOSTATIN
Action
 Somatostatin decreases gastrointestinal functions by decreasing motility, secretion and
absorption.
 It Inhibits secretion of gastrin and secretin.
 It decreases splanchnic blood flow.
 It decrease the release of Insulin and Glucagon.
 It also functions as neurotransmitter in Brain.
Pharmacokinetics
 Half life is 2-4 min
 Synthesized in two forms i.e. somatostatin-14 and somatostatin-28

SOMATOSTATIN
Pharmacokinetics
Half life is 2-4 min
Synthesized in two forms i.e. somatostatin-14 and somatostatin-28
Indication
Somatostatin analogs are used for treatment of tumors secreting vasoactive intestinal
peptide, carcinoid tumors, glucagonomas and various pituitary adenomas.
It is also used to treat acromegaly

SOMATOSTATIN
Adverse Effects
Steatorrhoea
Diarrhea and loose stools.
Malabsorption
Gastrointestinal cramps and occasional nausea.
Somatostatin inhibits gallbladder contractions, and some patients treated with
Sandostatin developed gallstones.

PANCREATIC POLYPEPTIDE (PP)
Pancreatic polypeptide (PP) is a polypeptide secreted by PP cells in the endocrine
pancreas predominatly in the head of pancreas.
It consists of 36 amino acids.
Action
The function of PP is to self-regulate pancreatic secretion activities.
It also has effects on hepatic glycogen levels and gastrointestinal secretions.

PANCREATIC POLYPEPTIDE (PP)
Plasma PP has been shown to be reduced in conditions associated with increased food
intake and elevated in anorexia nervosa.
Peripheral administration of PP has been shown to decrease food intake in rodents.. It
is the antagonist of CCK and inhibits the pancreatic secretion which is stimulated by
cholecystokinin.

GHRELIN
Ghrelin is a hormone that is produced and released mainly by the stomach with small
amounts also released by the epsilon cells of pancreas.
Ghrelin is termed the 'hunger hormone' because it stimulates appetite, increases food
intake and promotes fat storage.
Action
Ghrelin exerts wide physiological actions throughout the body, including growth
hormone secretion, appetite and food intake, gastric secretion and gastrointestinal
motility, glucose homeostasis, cardiovascular functions, anti-inflammatory functions,
reproductive functions, and bone formation.

Veterinary Pharmacology of Hormone secreted by pancreas

Veterinary Pharmacology of Hormone secreted by pancreas

More Related Content

Veterinary Pharmacology of Hormone secreted by pancreas