Type I Diabetes

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Type I Diabetes

• 
  
  by Jinbao Cao
• 
  
  Department of Chemistry
• 
  
  03/29/2011

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What is diabetes?
Diabetes is a group of diseases marked by high
levels of blood glucose resulting from defects in
insulin production, insulin action, or both.
Type 1 results from the body's failure to
produce insulin Type 2 results
from insulin resistance, a condition in
which cells fail to use insulin properly
Universal Symbol for Diabetes
Types of diabetes
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Introduction

• Current situation
• Diabetes affects 25.8 million people, 8.3 of U.S
  polulation
• Diabetes is the leading cause of kidney failure
• Diabetes is a major cause of heart disease and
  stroke
• Diabetes is the seventh leading cause of death
  in the United States

National Diabetes Fact Sheet, 2011
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National Diabetes Fact Sheet, 2011
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TYPE 1 Signs and Symptoms

• Polydipsia(increased thirst)
• Polyphagia(Increased hunger)
• Fatigue
• Weight loss
• Polyuria(frequent urination)

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Cause of Type 1 Dibetes
Genetic many different genes contribute to it
Vacor
Diet Wheat, Cows milk, Vitamin D, Brest milk
etc. Chemicals and Drugs Vacor, Zanosasr Virus
Enviromental
Zanosar
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Pathophysiology
Glucose concentration increase
Glucose concentration decrease
Insulin concentration increase
Activate Beta cell
convert glucose
Glucose concentration increase

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Diagnose

• Fasting plasma glucose level
• at or above 7.0mmol/L
• (126mg/dL)
• Plasma glucose at or above 11.1 mmol/L
• (200mg/dL) two hours after a 75 g oral
  
• glucoes load as in a glucose tolerance
  test

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Treatment

• Daily injection of insulin
• - Under skin
• - Before meal
• - Several times
• - Cant be swallowed
• Insulin pump
• Oral meditation Pramlintide (Symlin)
• Health diet fruits, vegetables, whole wheat
• Excise consume glucose

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New Methods

• Polymeric materials used as drug delivery
• Drugs can be bind to biodegradable polymer pedant
  groups, when polymer breaks down, drug will be
  released continuously
• Stimuli responsive polymers. Temperature, pH,
  glucose etc.

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Insulin

• A hormone regulating carbohydrate and fat
  metabolism in the body.
• Insulin causes cells in the liver, muscle, and
  fat tissue to take up glucose from the blood,
  storing it as glycogen in the liver and muscle.
• When insulin is absent, body begins to use fat as
  energy source. Lose weight, high blood glucose
  concentration

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Insulin history

• 1921 Frederick Banting and John Macleod first
  isolated insulin and successfully used to treat
  diabetes
• 1923 - MacLeod and Banting received Nobel Prize
  in Physiology and Medicine for insulin discovery
• 1955 Frederick Sanger won Nobel Prize in
  Chemistry for determining first order structure
  of insulin

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Primary Structure of Insulin

• Amino acid sequence

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Secondary Structure of Insulin

• Hydrogen bonding stabilizes insulin

Blue chain A Red chain B
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Tertiary Structure of Insulin

• Disulfide bond(yellow)
• -SH-SH S-S
• Disulfide bond formed
• Between 6 CYS residues
• Two disulfide bond between Chain A and Chain B,
  one between Chain A
• In addition salt bridge and
• Van de Waals force also exist

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Quaternary structure of Insulin

• Hydrophobic interaction
• between molecules
• General form in beta cell
• and blood
• Dimers also formed
• Active form is single molecular

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Synthesis of Insulin

• In vivo, produced within pancreas by b cells.
• Pig insulin and cattle insulin are very
  similar to human insulin
• Chinese scientists firstly synthesized insulin
  1965
• Today, insulin is mostly made biosynthetically by
  recombinant DNA technology or 'genetic
  engineering'.

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Release of Insulin

• First phase triggered by increase blood GLU
• -Glucose enters the ß-cells through the
  glucose transporter GLUT2
• -Glucose goes into glycolysis and the
  respiratory cycle, where multiple high-energy
  
• ATP molecules are produced by oxidation
• -Dependent on the ATPADP ratio, and hence
  blood glucose levels, the ATP-
• dependent potassium channels (K) close
  and the cell membrane depolarizes
• -On depolarization, voltage controlled
  calcium channels (Ca2) open and calcium
• flows into the cells
• -An increased calcium level causes
  activation of phospholipase C, which cleaves
• the membrane phospholipid phosphatidyl
  inositol 4,5-bisphosphate into inositol
• 1,4,5-triphosphate and diacylglycerol.
• -Inositol 1,4,5-triphosphate (IP3) binds
  to receptor proteins in the membrane of
• endoplasmic reticulum (ER). This allows
  the release of Ca2 from the ER via IP3
• gated channels, and further raises the
  cell concentration of calcium.
• -Significantly increased amounts of calcium
  in the cells causes release of previously
• synthesized insulin, which has been
  stored in secretory vesicles
• Second phase slowly release of newly formed
  insulin

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Oscillations

• Insulin release from pancreas is not continuous
• Oscillates within a period of 3-6min
• Concentration from 100pmol/L800pmol/L
• (A picomole is one-trillionth of a mole)
• Guidance for injection of insulin

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Degradation of Insulin

• Degraded one hour after release
• After work, either release back into
  extracellular environment or degraded by the cell
• Usually happens in liver or kindney

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Questions

• What are the difference between type 1 and type 2
  diabetes? To the level of the causes of two
  types.
• What are signs of type I diabetes?
• What is major force for the secondary structure
  of insulin?

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Assigned reading

• Goodman and Gillman, Chapter 43, pp. 1237-1254
  (large type only).
• Definition and diagnosis of diabetes mellitus and
  intermediate hyperglycemia
• (This a report of a WHO/IDF consultation,
  which introduces diabetes mellitus. You can read
  this report if you are interested. The precious
  questions are not based on this paper.)

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Reference

• http//en.wikipedia.org/wiki/Diabetes_mellitus_typ
  e_1
• http//en.wikipedia.org/wiki/Insulin
• National Diabetes Fact Sheet, 2011
• Jeffrey A. Bluestone1, Vol 464(29) April 2010,
  Nature
• Bart O. Roep, Diabetologia (2003) 46305321
• Definition and diagnosis of diabetes mellitus and
  intermediate hyperglycemia

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Thanks for Your Attention!
Questions?