Beta cell formation in vivo through cellular networking, integration and processing (CNIP) in wild type adult mice

Bruno Doiron, Wenchao Hu, Ralph A Defronzo

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Insulin replacement therapy is essential in type 1 diabetic individuals and is required in ~40- 50% of type 2 diabetics during their lifetime. Prior attempts at beta cell regeneration have relied upon pancreatic injury to induce beta cell proliferation, dedifferentiation and activation of the embryonic pathway, or stem cell replacement. We report an alternative method to transform adult non-stem (somatic) cells into pancreatic beta cells. The Cellular Networking, Integration and Processing (CNIP) approach targets cellular mechanisms involved in pancreatic function in the organ’s adult state and utilizes a synergistic mechanism that integrates three important levels of cellular regulation to induce beta cell formation: (i) glucose metabolism, (ii) membrane receptor function, and (iii) gene transcription. The aim of the present study was to induce pancreatic beta cell formation in vivo in adult animals without stem cells and without dedifferentiating cells to recapitulate the embryonic pathway as previously published (1-3). Our results employing CNIP demonstrate that: (i) insulin secreting cells can be generated in adult pancreatic tissue in vivo and circumvent the problem of generating endocrine (glucagon and somatostatin) cells that exert deleterious effects on glucose homeostasis, and (ii) longterm normalization of glucose tolerance and insulin secretion can be achieved in a wild type diabetic mouse model. The CNIP cocktail has the potential to be used as a preventative or therapeutic treatment or cure for both type 1 and type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)376-388
Number of pages13
JournalCurrent Pharmaceutical Biotechnology
Volume17
Issue number4
StatePublished - Mar 1 2016

Fingerprint

Insulin-Secreting Cells
Glucose
Stem Cells
Cell Dedifferentiation
Insulin
Adult Stem Cells
Somatostatin-Secreting Cells
Glucagon
Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
Regeneration
Homeostasis
Cell Proliferation
Membranes
Wounds and Injuries
Therapeutics
Genes

Keywords

  • Beta cell formation
  • In vivo
  • Insulin secretion

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Biotechnology

Cite this

Beta cell formation in vivo through cellular networking, integration and processing (CNIP) in wild type adult mice. / Doiron, Bruno; Hu, Wenchao; Defronzo, Ralph A.

In: Current Pharmaceutical Biotechnology, Vol. 17, No. 4, 01.03.2016, p. 376-388.

Research output: Contribution to journalArticle

@article{23575a5c6d1c4f89bdcf2ee3821093a2,
title = "Beta cell formation in vivo through cellular networking, integration and processing (CNIP) in wild type adult mice",
abstract = "Insulin replacement therapy is essential in type 1 diabetic individuals and is required in ~40- 50{\%} of type 2 diabetics during their lifetime. Prior attempts at beta cell regeneration have relied upon pancreatic injury to induce beta cell proliferation, dedifferentiation and activation of the embryonic pathway, or stem cell replacement. We report an alternative method to transform adult non-stem (somatic) cells into pancreatic beta cells. The Cellular Networking, Integration and Processing (CNIP) approach targets cellular mechanisms involved in pancreatic function in the organ’s adult state and utilizes a synergistic mechanism that integrates three important levels of cellular regulation to induce beta cell formation: (i) glucose metabolism, (ii) membrane receptor function, and (iii) gene transcription. The aim of the present study was to induce pancreatic beta cell formation in vivo in adult animals without stem cells and without dedifferentiating cells to recapitulate the embryonic pathway as previously published (1-3). Our results employing CNIP demonstrate that: (i) insulin secreting cells can be generated in adult pancreatic tissue in vivo and circumvent the problem of generating endocrine (glucagon and somatostatin) cells that exert deleterious effects on glucose homeostasis, and (ii) longterm normalization of glucose tolerance and insulin secretion can be achieved in a wild type diabetic mouse model. The CNIP cocktail has the potential to be used as a preventative or therapeutic treatment or cure for both type 1 and type 2 diabetes.",
keywords = "Beta cell formation, In vivo, Insulin secretion",
author = "Bruno Doiron and Wenchao Hu and Defronzo, {Ralph A}",
year = "2016",
month = "3",
day = "1",
language = "English (US)",
volume = "17",
pages = "376--388",
journal = "Current Pharmaceutical Biotechnology",
issn = "1389-2010",
publisher = "Bentham Science Publishers B.V.",
number = "4",

}

TY - JOUR

T1 - Beta cell formation in vivo through cellular networking, integration and processing (CNIP) in wild type adult mice

AU - Doiron, Bruno

AU - Hu, Wenchao

AU - Defronzo, Ralph A

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Insulin replacement therapy is essential in type 1 diabetic individuals and is required in ~40- 50% of type 2 diabetics during their lifetime. Prior attempts at beta cell regeneration have relied upon pancreatic injury to induce beta cell proliferation, dedifferentiation and activation of the embryonic pathway, or stem cell replacement. We report an alternative method to transform adult non-stem (somatic) cells into pancreatic beta cells. The Cellular Networking, Integration and Processing (CNIP) approach targets cellular mechanisms involved in pancreatic function in the organ’s adult state and utilizes a synergistic mechanism that integrates three important levels of cellular regulation to induce beta cell formation: (i) glucose metabolism, (ii) membrane receptor function, and (iii) gene transcription. The aim of the present study was to induce pancreatic beta cell formation in vivo in adult animals without stem cells and without dedifferentiating cells to recapitulate the embryonic pathway as previously published (1-3). Our results employing CNIP demonstrate that: (i) insulin secreting cells can be generated in adult pancreatic tissue in vivo and circumvent the problem of generating endocrine (glucagon and somatostatin) cells that exert deleterious effects on glucose homeostasis, and (ii) longterm normalization of glucose tolerance and insulin secretion can be achieved in a wild type diabetic mouse model. The CNIP cocktail has the potential to be used as a preventative or therapeutic treatment or cure for both type 1 and type 2 diabetes.

AB - Insulin replacement therapy is essential in type 1 diabetic individuals and is required in ~40- 50% of type 2 diabetics during their lifetime. Prior attempts at beta cell regeneration have relied upon pancreatic injury to induce beta cell proliferation, dedifferentiation and activation of the embryonic pathway, or stem cell replacement. We report an alternative method to transform adult non-stem (somatic) cells into pancreatic beta cells. The Cellular Networking, Integration and Processing (CNIP) approach targets cellular mechanisms involved in pancreatic function in the organ’s adult state and utilizes a synergistic mechanism that integrates three important levels of cellular regulation to induce beta cell formation: (i) glucose metabolism, (ii) membrane receptor function, and (iii) gene transcription. The aim of the present study was to induce pancreatic beta cell formation in vivo in adult animals without stem cells and without dedifferentiating cells to recapitulate the embryonic pathway as previously published (1-3). Our results employing CNIP demonstrate that: (i) insulin secreting cells can be generated in adult pancreatic tissue in vivo and circumvent the problem of generating endocrine (glucagon and somatostatin) cells that exert deleterious effects on glucose homeostasis, and (ii) longterm normalization of glucose tolerance and insulin secretion can be achieved in a wild type diabetic mouse model. The CNIP cocktail has the potential to be used as a preventative or therapeutic treatment or cure for both type 1 and type 2 diabetes.

KW - Beta cell formation

KW - In vivo

KW - Insulin secretion

UR - http://www.scopus.com/inward/record.url?scp=84959876261&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84959876261&partnerID=8YFLogxK

M3 - Article

VL - 17

SP - 376

EP - 388

JO - Current Pharmaceutical Biotechnology

JF - Current Pharmaceutical Biotechnology

SN - 1389-2010

IS - 4

ER -