INSULIN

Insulin was used in clinical
before
after
The development of Insulin
future 1996 insulin analogue
1978 human insulin 1973monocomponent insulin
1953 long lasting insulin 1946 NPH
Description
external insulin pump
Description
Implanted insulin pump
Long-term blood glucose sensor Real-time glucose meter
The third revolution of Insulin
The birth of Insulin
Frederick G. Banting Nobel Prize 1923 J.J.R Macleod Nobel Prize 1923
Charies H Best
James B Collip
1921年 —— Insulin extract from dog


Diabetes is growing Chinese diabetes patients is NO.1
2013: 382 millions diabetes patients in the world 2035: 592 millions diabetes patients in the world IDF, 2013 Top countries of number of people with diabetes（20~79岁） China is NO.1（millions）
Insulin injection
MDI (multiple daily injections )
CSII (continuous subcutaneous insulin infusion)
Insulin Pump
2000 1998 1996
Future: Artificial Pancreas
Oral Insulin or other?
Analogue
recombinant insulin
胰岛素类似物
Insulin purification
人胰岛素
Long lasting Insulin
Qualification for production
No injection: oral ?
The challenge of oral insulin
absorb
aberrance
Pancreas Island Transplantation
Thank for your attention
By acid hydrolysis
enzymatic degradation
Mucus/mucosa / Permeability/barrier By pancreatic enzyme degradation By enzyme degradation of mucus
pH
food transit time
75 Breakfast Lunch Dinner
Plasma Insulin 50 (U/mL)
short 25 long short short
0
4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00
Time
Skyler J, Kelley’s Textbook of Internal Medicine 2000.
The birthday of Banting, 14th Nov, was classified as The World Diabetes Day
The first Person
1rd, Jan, 1922 14–year-old, girl The fisrt person Died at age of 27
Description: Automatically reads glucose levels and administers insulin infusion Referred to as “Closed-Loop” System(闭环胰岛素泵）
+
external system
+
implanted system
INSULIN
past, now, future
The Third People’s Hospital onow insulin

The hormone that people most familiar with
Diabetes Mellitus: insulin deficiency Diabetes becomes one of most common disease
1923 animal insulin
1920 1930 1940 1950 1960 1970 1980 1990 2000
The first revolution of Insulin
recombinant insulin
Solve the problem of immunogenicity
Human Insulin In 1978

Short Lasting Human Insulin Peak isn’t high enough, and rate isn’t fast enough

NPH (Neutral Protamine Hagedorn ,中性鱼精蛋白胰岛素）
Baseline Insulin, but is not longer and stable enough
Karsholm & Ludvigsen. Receptor 1995;5:1-8.
Insulin Analogue
Insulin Analogue
Physiological Insulin Secretion Premix Human Insulin
Aspart ® 30 诺和锐®30
Injection: multiple daily injections
生理胰岛素曲线
Short lasting Human Insulin NPH Premix Human Insulin
The second revolution of Insulin
Analogue
Simulation of the physiological model
recombinant insulin
/worlddiabetescongress
Diabetes Mellitus
Insulin deficiency
Insulin Resistance
Diabetes Mellitus
Function of insulin



Insulin (from the Latin, insula meaning island) is a peptide hormone produced by beta cells in the pancreas Control of cellular intake of certain substances, most prominently glucose in muscle and adipose tissue (about two-thirds of body cells) Increase of DNA replication and protein synthesis via control of amino acid uptake Modification of the activity of numerous enzymes It is the only hormone which descend glucose Glucose is the most direct energy in our body
wwwidforgworlddiabetescongressidf2013topcountriesofnumberofpeoplewithdiabetes2079岁chinaisno1millionsdiabetesmellitusdiabetesmellitusinsulindeficiencyinsulinresistancefunctionofinsulin?insulinfromthelatininsulameaningislandisapeptidehormoneproducedbybetacellsinthepancreas?controlofcellularintakeofcertainsubstancesmostprominentlyglucoseinmuscleandadiposetissueabouttwothirdsofbodycells?increaseofdnareplicationandproteinsynthesisviacontrolofaminoaciduptake?modificationoftheactivityofnumerousenzymes?itistheonlyhormonewhichdescendglucose?glucoseisthemostdirectenergyinourbodyjamesbcollipfrederickgbantingnobelprize1923charieshbestjjrmacleodnobelprize19231921年insulinextractfromdogthebirthofinsulinthebirthdayofbanting14thnovwasclassifiedastheworlddiabetesdaythefirstpersonafterbefore1rdjan192214yearoldgirlthefisrtpersondiedatageof27insulinwasusedinclinical1923animalinsulin1920193019401950196019701980199020001973monocomponentinsulin1978humaninsulin1996insulinanalogue1946nph1953longlastinginsulinfuturethedevelopmentofinsu
Insulin purification
Long Lasting Insulin Animal Insulin
Qualification for production
Human Insulin

Physiological insulin secretion curve:
Baseline
Meal Bolus
Insulin Analogue In 1996
Insulin purification
Human Insulin
Long lasting Insulin
Qualification for production
insulin Insulin lispro Glargine —— Pro B replace chain and Lys plus exchange 2 ， super A21: short Gly lasting replace lasting Asp Insulin Aspart B28: Asp Pro ，Arg super short Insulin Detemir del B30 ，B29 plus tetradecanoic acid Long lasting Long lasting Phe Gly Arg B28 Tyr Phe Glu Thr B29 Gly Asp Pro Cys A21 Lys B30 Val Thr Gly Asn Cys Tyr Leu A1 Arg Asn Tyr gly Arg Glu Leu Ile Leu Ala Val Gln Glu Glu Tyr Gln Val Leu Cys Ser Leu Cys Thr Ser Ile Cys His Ser Gly Cys B1 Phe Val Asn Gln His Leu