10.8.2007 diasoce3.ppt 1 Why is the current therapy not perfect? Even slightly elevated blood glucose is harmful. The limiting factor of insulin treatment is hypoglycaemia. The compensation of disease is despite intensified treatment, new insulins (rapid and slow analogues) and pump treatment is often not sufficient – Peripheral/portal insulin – Lack of C-peptide (?!) – Lack of paracrine regulation – The human factor (doctor, patient)
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10.8.2007diasoce3.ppt1 Why is the current therapy not perfect? Even slightly elevated blood glucose is harmful. The limiting factor of insulin treatment.
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10.8.2007 diasoce3.ppt 1
Why is the current therapy not perfect?
Even slightly elevated blood glucose is harmful. The limiting factor of insulin treatment is hypoglycaemia. The compensation of disease is despite intensified
treatment, new insulins (rapid and slow analogues) and pump treatment is often not sufficient– Peripheral/portal insulin– Lack of C-peptide (?!)– Lack of paracrine regulation– The human factor (doctor, patient)
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Possibilities
Pancreas transplantation Islet cell transplantation B cells from stem cells Genetically modified cells producing
insulin Regeneration of B cells Arteficial Langerhans islets
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Real possibilities
Pancreas transplantation (yes) Islet cell transplantation (yes, but) B cells from stem cells (research) Genetically modified cells producing insulin
(yes, but not for direct treatment) Regeneration of B cells (???) Closed loop system – pump and senzor (yes, but) Arteficial islets (research)
– Good results of autotransplantations– Minimally invasive surgery (1 day)– Isolated islets can be stored
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Stem cells
Embryonal cells – ethical problem Adult – rapid progress in the last years. Stem cells for
islets can be found among ductal epithel cells Therapeutical cloning – technological problems and
legislative hurdles Study of islet ontogenesis (very complicated) Exact role of transcription factors
– INGAP is a purified protein, in experiment lowers BG, activates other factors of islet development
– Pdx1 k.o. mouse is born without pancreas. But Pdx1 is exprimoved also in adult age. K.o. leads to diabetes – more A than B cells, insufficient expression of GLUT2. The cause of MODY 4
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Regeneration of pancreas
Brunner Korec, Šofranková (but also we) Don’t believe the professors! (the cells of
endocrine glands do not divide) They divide - apoptosis and regeneration
of B cells is intensive Disturbed balance – T1 and T2DM
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Yeasts and bacteria produce insulin
In tanks of Eli Lilly (yeast) and NOVO-NORDISK (E. coli), but not in our body
(The problem of regulation) Majority of diabetics is on human insulins Genetic engineering (exchange of
aminacids) rapid and very slow insulin analogues
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Closed loop systemsBioarteficial pancreas
Strips in glucometers produce color or electrical signal
Continuous glucose measurement (3 -5 days)
Insulin pumps are at hand Connect them together The first biostator was constructed in 1972 Does not work for long term and safely