Beta testingMarjan Slak Rupnik

University of MariborCentre of excellence for integrated approaches to chemistry and

biology of proteins

Beta testing- addressing key obstacles reducing the quality of life- diseases – example: diabetes mellitus- described for many centuries, treated during the last,

but despite that in epidemic expansion- missing critical puzzle pieces – beta testing

Innovative ways out...- understanding human physiology or systems

biology outside the context of a modern civilization (e.g. medicine and industry)- an organism is not stupid and helpless

- understanding pathophysiology- concepts and leading researchers can be

wrong- stop avoiding the obvious

What is diabetes mellitus?

- polyuria in polydipsia- hyperglycemia

- not enough beta cells to produce insulin (T1DM; autoimmune, viral,...)

- body simply too big for the maximal insulin production (T2DM; obesity, predisposition to low beta cell mass,...)

- the solution to remove signs is too simple: use of insulin to lower glucose and stop osmotic diuresis

Endocrine pancreas

5

Glucose-dependent insulin release

- the primary role of insulin is not to reduce blood glucose (industrial definition).

The role of insulin is anabolic,it is in fact a growth hormone

insulin resistance

Keeping the plasma glucose levelhigh enough

-not enough beta cells to produce insulin (T1DM) – insulin sensitive-body simply too big for the maximal insulin production (T2DM) – insulin insensitive

Why misconceptions?

• individual cells• coupled beta-cell clusters• neural control of coupled

clusters

9

insulin

acetylcholine

Pancreas innervation

- peripheral neuropathy – a consequence or a cause

Different patterns of insulin release

10 mM glucose

oral

IV

N

D

Consensus model insulin secretion (beta version)

1 2

3

CSI Maribor

high spatial resolution of indicator loaded cells

clear identification of ROI of individual beta cell

clear identification of ROI of individual non-beta cell

1 2

Alternative model of Ca2+ regulation in a beta cell

Malignant hyperthermia – porcine stress syndrome

When Pigs Stress OutBy ARMELLE CASAUPublished: October 07, 2003

Half a century of selective breeding has had an unappetizing side effect for the nation's $40 billion-a-year pork industry.In what researchers say is a biochemical chain reaction sometimes caused by a stress syndrome inadvertently bred into many pigs, 10 to 15 percent of pork turns into sweating pale cuts of meat that ooze liquid in the packaging and become leathery when cooked.The pork industry estimates that the problem costs $90 million a year in lost revenue. Now the losses have led to research to seek new ways to improve breeding and handling.Food scientists say the problem dates from the 1950's,

when breeders started selecting pigs with increased mass of lean muscle. Those pigs, it turned out, also

inherited a naturally occurring condition, porcine stress syndrome.As farmers bred faster-growing hogs with ultralarge, ultralean muscles that could compete as ''the other white meat,'' they were inadvertently selecting for the syndrome, said Dr. Jodi Sterle, a swine specialist at Texas A&M University...

I know I can die of stress due to hyperthermia, but

why is my lean muscle mass so big?

European Neuroscience Institute Göttingen (ENI-G) is jointly funded by Medical faculty of University of Goettingen, Max-Planck Society and Schering AG. Institute of Physiology was a Partner Group to Max-Planck Institute for biophysical Chemistry, Göttingen.

Bark C, Berggren P-O, Efendić S, Karolinska InstituteShen Y, Zhijiang University, HangzhouGaisano H, U TorontoWalther D, MPI Molecular Genetics Berlin