The endocrine pancreas & the control of blood glucose

The pancreas is both an endocrine & exocrine gland This endocrine gland produces hormones which are secreted from cells located in the islets of Langerhans or B cells produce Insulin 2 or A cells produce Glucagon

These hormones play an important role to maintain homeostasis of blood glucose

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 The effect of insulin on blood glucose:

1. glucose uptake 2. glycogen synthesis 3. glycogenolysis 4. gluconeogenisis

Main effect blood glucose

Acute rise in blood glucose is the main stimulus for insulin secretion

Glucose balance in the body

 Relative or absolute lack of insulin can cause hyperglycemia (Diabetes Mellitus: DM) DM is a chronic metabolic disorder characterized by a high blood glucose concentration Fasting plasma glucose 7.0 mmol/L(126 mg/dl) random (plasma glucose > 11.0 mmol/L (200mg/dl)

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 When the renal threshold for glucose, exceeded (>180mg/dl) glucose spills over into urine (Glycosuria) & loss of H2O (Polyuria) which in turn results in dehydration, thirst & drinking (Polydipsia)

 Insulin deficiency causes wasting through increased breakdown & reduced synthesis of proteins Absolute lack of insulin Adipose tissues Lipolysis Fatty acids weight loss Liver Metabolism Formation of ketone bodies -OH-butyric acid Acetoacetate Blood Cause Ketoacidosis 7

 Various complications develop as a sequence of this metabolic disorder

1.Retinopathy 2.Neuropathy 3.Nephropathy 3.Macrovascular disease

Consequences of poor management of DM

Microvascular complications

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Macrovascular complications

Diabetics: 2-4 x higher risk for MI, CVA

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 DM can be divided to: Type I: Insulin Dependent DM (IDDM) Type II: Non-Insulin Dependent DM (NIDDM) Type III (Gestational DM)

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Age of onset Pathogenesis

Pancreatic function

IDDM Usually < 30 years Loss of -cells function may be due to viruses, or autoimmune antibodies that cause destruction of -cells Complete insulin deficiency

NIDDM Usually > 40 years No evidence of immune disease - Tissue resistance to insulin Relative insulin deficiency

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IDDM Clinical picture Moderate-severe symptoms: Polyuria, Polydipsia - Weight loss - Develop Ketoacidosis Always need insulin Diet, exercise modification

NIDDM Mild Polyuria & fatigue - Obese - Develop none ketotic state

treatment

Weight reduction - Exercise, diet modification - Oral hypoglycemic agents - Insulin may be 14 required

Major factors contributing to hyperglycemia observed in Type 2 diabetes

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Type I DM Treatment
Exogenous Insulin control hyperglycemia prevent DKA

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Ultimate Goal of Insulin Treatment

Maintain BGL close to normal as possible Prevent fluctuations in BGL Prevent or delay long-term complications

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 Insulin Pharmacokinetic aspects & insulin preparations: Insulin as a small protein consisting of 2 polypeptide chains It is destroyed in GIT (because it is protein) if it is given orally, so given parentrally usually S.C. but I.V. for emergencies Insulin has t: 10 minutes, so it has short duration of action
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Structure of human insulin

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Sources of Insulin It is available in many preparation which vary in both onset & duration of action. Insulin was extracted from pancreas of cows (bovine) or pigs (pork) Now it is possible to produce human insulin either modifying pork insulin or by recombinant method involving bacteria Various formulation are available, varying in their onset & duration of action E.g.: Long acting preparations are made by precipitating insulin with Protamine or zinc (insoluble crystals from which insulin is 20 slowly absorbed)

Insulin Preparations
1.Ultra short Insulin lispro 2.Short acting Regular insulin Soluble crystalline zinc insulin Also used I.V. for emergency (Ketoacidosis)

3.Intermediate acting NPH, lente insulin

4.Long actinginsulin glargine, ultralente insulin

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Strength of insulin preparation

Insulin dose is monitored by units not by mg There are special syringes for insulin All insulin are now of standard strength 100 units in 1 mL The 100u syringes are marked in units of insulin & so it is only necessary to draw up the required # of units Insulin should be stored in refrigerator (not freezing compartment), but the bottle in current use can be safely kept at room 22 temperature

 Injection of Insulin
Most patients receiving insulin are instructed how to inject themselves The best sites for injections are: 1. Front of the thighs 2. Outer side of the upper arm

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Insulin Administration

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Monitoring Blood Glucose

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 Unwanted effects A. The main undesirable effects of insulin is hypoglycemia

Symptoms of hypoglycemia 1. Tachycardia 2. Sweating 3. Confusion 4. Tremor 5. Blurred vision

If the patient develops hypoglycemia & he did not eat sugar, he might develop hypoglycemic coma that may lead to brain damage & death 26

Hypoglycemia occurs: Skipping a meal Delaying a meal Exercise pattern (did severe exercise) Dose of insulin To correct hypoglycemia 1. Take sweet drink or snack 2. If the patient is unconscious I.V. glucose or I.M. glucagon

B. Allergic reactions C. Atrophic changes of the skin D. Weight gain.

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 Adverse effects observed with insulin

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 Oral hypoglycemic agents These agents are useful for NIDDM as a supplement to diet & exercise to control hyperglycemia sulfonylureas Available agents MOA S/Es Other comments Glyburide, glipizide Stimulate insulin secretion Hypoglycemia, wt gain C/I: hepatic or renal impairment biguanides metformin hepatic glucose output GI (nausea, bloating) Does not stimulate appetite, Does not cause hypoglycemia
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meglitinides
Available agents MOA repaglinide Stimulate insulin secretion

-glucosidase inhibitors acarbose

Delay carbohydrate absorption

Thiazolidinediones
pioligtazone Decrease insulin resistance Risk of hepatotoxicity. wt gain

S/Es

Hypoglycemia diarrhea wt gain

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 Implications for dentistry A number of oral complications may occur in diabetes These include xerostomia, infection, poor healing of wounds or lesions & increased incidence & severity of caries, candidiasis, gingivitis, & may have progressive periodontal disease. Through evaluation of the mouth followed by controlled oral hygiene program- including regular oral examination, professional cleanings & plaque control are recommended.

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