Lecture Slides German

8/13/2019 Lecture Slides German

1/16

Diabetes: Diagn

Treatment, and Opportun

Michael German, MD

Professor of Medicine

UC San Francisco

Module 5: Frontiers and N


2/16

Birth and Death of the Beta


3/16

Introduction: Michael German

MDo Dr. Michael German, Professor of Medi

Clinical Director of the UCSF Diabetes C

o Teaches Diabetes, Endocrinology andMetabolism to students, residents, fello

patients.o Directs a research program on the biolo

the pancreatic beta cell.


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Learning Objectives

o The importance of beta-cell mass in dia

o The origins of beta cells during develop

and in adult patients

o Signals that control beta cell numbers

o Challenges in increasing beta cell mass

o Future approaches to beta cell mass ex


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The Pancreatic Beta Cell


6/16

Role of the Beta Cell in Diab

o Type 1 diabetes:

Absolute beta cell deficiency

o Type 2 diabetes:

Relative beta cell deficiency due to inabeta cell mass or function usually in th

of increased insulin demand


7/16

Where Do Beta Cells Come F


8/16


Adrenal (cortisol, epinephrine)Adipose (leptin, adiponectin)Gut (GLP1, GIP, gastrin)Bone (osteocalcin)Liver (betatrophin)Pituitary (GH, Prl)Placenta (PL)

Metabolic Auto/Paracrin

Neural

Glucose

LipidsIslet

Ins

IAIGN

UGAVE

PDG

ParasympatheticSympathetic

SensoryEnteric

Endocrine

ATPAdenosineSerotoninDopamine

Acetylcholine


9/16

When Does Beta Cell Mass Ch

o Expansion:

Perinatal Pregnancy

Obesity

o Contraction

Postpartum Starvation

Insulinoma


10/16

The Beta Cell during Pregna

-cell

Placenta

PRLR

HTR2B

prolife

5HTTPH

Trp


11/16

The Beta Cell during Pregna

-cell

Placenta

HTR1D

PRLR

prolife

5HTTPH

Trp


12/16




Neural

Glucose

Lipids Islet

Ins

IAIGN

UGAVE

PDG


SensoryEnteric

Endocrine


Acetylcholine


13/16

How Do We Apply This to Pat

o Beta cell expansion is especially critical

pregnancy and the perinatal period.

o Drugs that impact beta cell proliferatio

death.

o Environmental factors that impact beta

proliferation and death.


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Challenges to Human Applica

o Limitations in our knowledge of human be

turnover. All based on pathologic samples

No way to measure beta cell mass, proliferati

death in humans in vivo.

o No clear evidence that any current therap

either protect or expand beta cell mass in


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How Do We Apply This to Pat

o Beta cell replacement.

o Beta cell protection.

o Beta cell expansion in vitro.

o Beta cell expansion in vivo.


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Neural

Glucose

Lipids Islet

Ins

IAIGN

UGAVE

PDG


SensoryEnteric

Endocrine


Acetylcholine

Documents

Lecture Slides German