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The endocrine pancreas & the control ofblood glucose

– The pancreas is both an endocrine & exocrine gland– This endocrine gland produces hormones which are

secreted from cells located in the islets ofLangerhans

• β or B cells produce Insulin • α2 or A cells produce Glucagon

– These hormones play an important role to maintainhomeostasis of blood glucose

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• The effect of insulin on blood glucose:

1.↑ glucose uptake2.↑ glycogen synthesis3.↓ glycogenolysis

4.↓

gluconeogenisis

Acute rise in blood glucose is the main stimulusfor insulin secretion

Main effect ↓ blood glucose

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Glucosebalance in the

body

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• Relative or absolute lack of insulin can causehyperglycemia (Diabetes Mellitus: DM)

• DM is a chronic metabolic disorder characterizedby 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 spillsover into urine (Glycosuria)& loss ofH2O (Polyuria) which in turn results indehydration, thirst & ↑ drinking (Polydipsia)

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– Insulin deficiency causes wasting through increasedbreakdown & reduced synthesis of proteins

Absolute lack of insulin↓ Adipose tissues

↓ LipolysisFatty acids weight loss

↓ Liver

↓ Metabolism

↓ Formation of ketone bodies → β-OH-butyric acid

↓ → AcetoacetateBlood

↓

Cause Ketoacidosis

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• Various complications develop as a sequence of thismetabolic disorder

1.Retinopathy2.Neuropathy3.Nephropathy3.Macrovascular disease

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Consequences of poor management

of DM

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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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NIDDMIDDMUsually > 40 yearsUsually < 30 yearsAge of onset No evidence ofimmune disease - Tissueresistance toinsulin

Loss of β -cellsfunction may bedue to viruses, orautoimmuneantibodies thatcause destructionof β -cells

Pathogenesis

Relative insulindeficiency

Complete insulindeficiency

Pancreaticfunction

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NIDDMIDDMMild Polyuria &fatigue - Obese - Develop noneketotic state

Moderate-severesymptoms:Polyuria,Polydipsia - Weight loss - DevelopKetoacidosis

Clinical picture

Weight reduction - Exercise, dietmodification - Oralhypoglycemicagents - Insulin may berequired

Always needinsulinDiet, exercisemodification

treatment

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Major factors contributing to hyperglycemiaobserved 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 2polypeptide chains

• It is destroyed in GIT (because it isprotein) if it is given orally, so givenparentrally usually S.C. but I.V. for

emergencies• Insulin has t½: 10 minutes, so it has shortduration of action

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Structure of human insulin

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Sources of Insulin

• It is available in many preparation whichvary in both onset & duration of action.Insulin was extracted from pancreas ofcows (bovine) or pigs (pork)

• Now it is possible to produce human insulineither modifying pork insulin or byrecombinant method involving bacteria

• Various formulation are available, varying intheir onset & duration of action

E.g. : Long acting preparations are made byprecipitating insulin with Protamine or zinc(insoluble crystals from which insulin isslowly absorbed)

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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 acting→ insulin 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 ofinsulin & so it is only necessary to draw up therequired # of units

•Insulin should be stored in refrigerator (notfreezing compartment), but the bottle incurrent use can be safely kept at roomtemperature

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• Injection of Insulin

• Most patients receiving insulin are instructedhow to inject themselves

• The best sites for injections are: 1. Front of the thighs2. 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. Sweating3. Confusion4. Tremor5. Blurred vision

• If the patient develops hypoglycemia & he didnot eat sugar, he might develop hypoglycemic

coma that may lead to brain damage & death

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Hypoglycemia occurs:• Skipping a meal• Delaying a meal• Exercise pattern (did severe exercise)• Dose of insulin

• To correct hypoglycemia1. Take sweet drink or snack2. If the patient is unconscious I.V.

glucose or I.M. glucagon

B. Allergic reactionsC. Atrophic changes of the skinD. Weight gain.

Ad ff b d i h i li

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• Adverse effects observed with insulin

• Oral hypoglycemic agents

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• Oral hypoglycemic agentsThese agents are useful for NIDDM as a supplement to

diet & exercise to control hyperglycemia

biguanidessulfonylureasmetforminGlyburide,

glipizideAvailable agents

↓ hepatic glucoseoutputStimulate insulinsecretionMOA

GI (nausea, bloating)Hypoglycemia, wtgain

S/Es

Does not stimulateappetite, Does notcause hypoglycemia

C/I: hepatic orrenal impairment

Other comments

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Thiazolidinedionesα-glucosidaseinhibitors

meglitinides

pioligtazoneacarboserepaglinideAvailableagents

Decrease insulin

resistance

Delay

carbohydrateabsorption

Stimulate

insulinsecretion

MOA

Risk ofhepatotoxicity.

wt gain

diarrheaHypoglycemiawt gain

S/Es

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• Implications for dentistry

A number of oral complications may occur in diabetesThese include xerostomia, infection, poor healing ofwounds or lesions & increased incidence & severity ofcaries, candidiasis, gingivitis, & may have progressiveperiodontal disease.

Through evaluation of the mouth followed by controlledoral hygiene program- including regular oralexamination, professional cleanings & plaque controlare recommended .

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