Review Series 10.1172/JCI142240

Normal and defective pathways in biogenesis and maintenance of the insulin storage pool

Ming Liu,1 Yumeng Huang,1,2 Xiaoxi Xu,1,2 Xin Li,1 Maroof Alam,2 Anoop Arunagiri,2 Leena Haataja,2 Li Ding,1 Shusen Wang,3 Pamela Itkin-Ansari,4 Randal J. Kaufman,5 Billy Tsai,6 Ling Qi,7 and Peter Arvan2

1Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.

2Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan, USA.

3Organ Transplant Center, Tianjin First Central Hospital, Tianjin, China.

4Development, Aging and Regeneration Program, and

5Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.

6Department of Cell and Developmental Biology, and

7Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.

Address correspondence to: Peter Arvan, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Brehm Tower, 1000 Wall Street, Ann Arbor, Michigan 48105, USA. Phone: 734.936.5505; Email: parvan@umich.edu. Or to: Ming Liu, Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, 154 Ann Anshan Road, Heping District, Tianjin 300052, China. Email: mingliu@tmu.edu.cn.

Find articles by Liu, M. in: JCI | PubMed | Google Scholar |

1Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.

2Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan, USA.

3Organ Transplant Center, Tianjin First Central Hospital, Tianjin, China.

4Development, Aging and Regeneration Program, and

5Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.

6Department of Cell and Developmental Biology, and

7Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.

Address correspondence to: Peter Arvan, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Brehm Tower, 1000 Wall Street, Ann Arbor, Michigan 48105, USA. Phone: 734.936.5505; Email: parvan@umich.edu. Or to: Ming Liu, Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, 154 Ann Anshan Road, Heping District, Tianjin 300052, China. Email: mingliu@tmu.edu.cn.

Find articles by Huang, Y. in: JCI | PubMed | Google Scholar

1Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.

2Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan, USA.

3Organ Transplant Center, Tianjin First Central Hospital, Tianjin, China.

4Development, Aging and Regeneration Program, and

5Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.

6Department of Cell and Developmental Biology, and

7Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.

Address correspondence to: Peter Arvan, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Brehm Tower, 1000 Wall Street, Ann Arbor, Michigan 48105, USA. Phone: 734.936.5505; Email: parvan@umich.edu. Or to: Ming Liu, Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, 154 Ann Anshan Road, Heping District, Tianjin 300052, China. Email: mingliu@tmu.edu.cn.

Find articles by Xu, X. in: JCI | PubMed | Google Scholar

1Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.

2Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan, USA.

3Organ Transplant Center, Tianjin First Central Hospital, Tianjin, China.

4Development, Aging and Regeneration Program, and

5Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.

6Department of Cell and Developmental Biology, and

7Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.

Address correspondence to: Peter Arvan, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Brehm Tower, 1000 Wall Street, Ann Arbor, Michigan 48105, USA. Phone: 734.936.5505; Email: parvan@umich.edu. Or to: Ming Liu, Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, 154 Ann Anshan Road, Heping District, Tianjin 300052, China. Email: mingliu@tmu.edu.cn.

Find articles by Li, X. in: JCI | PubMed | Google Scholar

1Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.

2Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan, USA.

3Organ Transplant Center, Tianjin First Central Hospital, Tianjin, China.

4Development, Aging and Regeneration Program, and

5Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.

6Department of Cell and Developmental Biology, and

7Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.

Address correspondence to: Peter Arvan, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Brehm Tower, 1000 Wall Street, Ann Arbor, Michigan 48105, USA. Phone: 734.936.5505; Email: parvan@umich.edu. Or to: Ming Liu, Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, 154 Ann Anshan Road, Heping District, Tianjin 300052, China. Email: mingliu@tmu.edu.cn.

Find articles by Alam, M. in: JCI | PubMed | Google Scholar |

1Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.

2Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan, USA.

3Organ Transplant Center, Tianjin First Central Hospital, Tianjin, China.

4Development, Aging and Regeneration Program, and

5Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.

6Department of Cell and Developmental Biology, and

7Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.

Address correspondence to: Peter Arvan, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Brehm Tower, 1000 Wall Street, Ann Arbor, Michigan 48105, USA. Phone: 734.936.5505; Email: parvan@umich.edu. Or to: Ming Liu, Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, 154 Ann Anshan Road, Heping District, Tianjin 300052, China. Email: mingliu@tmu.edu.cn.

Find articles by Arunagiri, A. in: JCI | PubMed | Google Scholar |

1Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.

2Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan, USA.

3Organ Transplant Center, Tianjin First Central Hospital, Tianjin, China.

4Development, Aging and Regeneration Program, and

5Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.

6Department of Cell and Developmental Biology, and

7Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.

Address correspondence to: Peter Arvan, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Brehm Tower, 1000 Wall Street, Ann Arbor, Michigan 48105, USA. Phone: 734.936.5505; Email: parvan@umich.edu. Or to: Ming Liu, Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, 154 Ann Anshan Road, Heping District, Tianjin 300052, China. Email: mingliu@tmu.edu.cn.

Find articles by Haataja, L. in: JCI | PubMed | Google Scholar |

1Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.

2Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan, USA.

3Organ Transplant Center, Tianjin First Central Hospital, Tianjin, China.

4Development, Aging and Regeneration Program, and

5Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.

6Department of Cell and Developmental Biology, and

7Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.

Address correspondence to: Peter Arvan, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Brehm Tower, 1000 Wall Street, Ann Arbor, Michigan 48105, USA. Phone: 734.936.5505; Email: parvan@umich.edu. Or to: Ming Liu, Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, 154 Ann Anshan Road, Heping District, Tianjin 300052, China. Email: mingliu@tmu.edu.cn.

Find articles by Ding, L. in: JCI | PubMed | Google Scholar |

1Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.

2Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan, USA.

3Organ Transplant Center, Tianjin First Central Hospital, Tianjin, China.

4Development, Aging and Regeneration Program, and

5Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.

6Department of Cell and Developmental Biology, and

7Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.

Address correspondence to: Peter Arvan, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Brehm Tower, 1000 Wall Street, Ann Arbor, Michigan 48105, USA. Phone: 734.936.5505; Email: parvan@umich.edu. Or to: Ming Liu, Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, 154 Ann Anshan Road, Heping District, Tianjin 300052, China. Email: mingliu@tmu.edu.cn.

Find articles by Wang, S. in: JCI | PubMed | Google Scholar

1Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.

2Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan, USA.

3Organ Transplant Center, Tianjin First Central Hospital, Tianjin, China.

4Development, Aging and Regeneration Program, and

5Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.

6Department of Cell and Developmental Biology, and

7Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.

Address correspondence to: Peter Arvan, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Brehm Tower, 1000 Wall Street, Ann Arbor, Michigan 48105, USA. Phone: 734.936.5505; Email: parvan@umich.edu. Or to: Ming Liu, Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, 154 Ann Anshan Road, Heping District, Tianjin 300052, China. Email: mingliu@tmu.edu.cn.

Find articles by Itkin-Ansari, P. in: JCI | PubMed | Google Scholar

1Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.

2Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan, USA.

3Organ Transplant Center, Tianjin First Central Hospital, Tianjin, China.

4Development, Aging and Regeneration Program, and

5Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.

6Department of Cell and Developmental Biology, and

7Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.

Address correspondence to: Peter Arvan, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Brehm Tower, 1000 Wall Street, Ann Arbor, Michigan 48105, USA. Phone: 734.936.5505; Email: parvan@umich.edu. Or to: Ming Liu, Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, 154 Ann Anshan Road, Heping District, Tianjin 300052, China. Email: mingliu@tmu.edu.cn.

Find articles by Kaufman, R. in: JCI | PubMed | Google Scholar |

1Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.

2Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan, USA.

3Organ Transplant Center, Tianjin First Central Hospital, Tianjin, China.

4Development, Aging and Regeneration Program, and

5Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.

6Department of Cell and Developmental Biology, and

7Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.

Address correspondence to: Peter Arvan, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Brehm Tower, 1000 Wall Street, Ann Arbor, Michigan 48105, USA. Phone: 734.936.5505; Email: parvan@umich.edu. Or to: Ming Liu, Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, 154 Ann Anshan Road, Heping District, Tianjin 300052, China. Email: mingliu@tmu.edu.cn.

Find articles by Tsai, B. in: JCI | PubMed | Google Scholar

1Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.

2Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan, USA.

3Organ Transplant Center, Tianjin First Central Hospital, Tianjin, China.

4Development, Aging and Regeneration Program, and

5Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.

6Department of Cell and Developmental Biology, and

7Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.

Address correspondence to: Peter Arvan, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Brehm Tower, 1000 Wall Street, Ann Arbor, Michigan 48105, USA. Phone: 734.936.5505; Email: parvan@umich.edu. Or to: Ming Liu, Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, 154 Ann Anshan Road, Heping District, Tianjin 300052, China. Email: mingliu@tmu.edu.cn.

Find articles by Qi, L. in: JCI | PubMed | Google Scholar |

1Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.

2Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan, USA.

3Organ Transplant Center, Tianjin First Central Hospital, Tianjin, China.

4Development, Aging and Regeneration Program, and

5Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.

6Department of Cell and Developmental Biology, and

7Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.

Address correspondence to: Peter Arvan, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Brehm Tower, 1000 Wall Street, Ann Arbor, Michigan 48105, USA. Phone: 734.936.5505; Email: parvan@umich.edu. Or to: Ming Liu, Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, 154 Ann Anshan Road, Heping District, Tianjin 300052, China. Email: mingliu@tmu.edu.cn.

Find articles by Arvan, P. in: JCI | PubMed | Google Scholar |

Published January 19, 2021 - More info

Published in Volume 131, Issue 2 on January 19, 2021
J Clin Invest. 2021;131(2):e142240. https://doi.org/10.1172/JCI142240.
© 2021 American Society for Clinical Investigation
Published January 19, 2021 - Version history
View PDF

Both basal and glucose-stimulated insulin release occur primarily by insulin secretory granule exocytosis from pancreatic β cells, and both are needed to maintain normoglycemia. Loss of insulin-secreting β cells, accompanied by abnormal glucose tolerance, may involve simple exhaustion of insulin reserves (which, by immunostaining, appears as a loss of β cell identity), or β cell dedifferentiation, or β cell death. While various sensing and signaling defects can result in diminished insulin secretion, somewhat less attention has been paid to diabetes risk caused by insufficiency in the biosynthetic generation and maintenance of the total insulin granule storage pool. This Review offers an overview of insulin biosynthesis, beginning with the preproinsulin mRNA (translation and translocation into the ER), proinsulin folding and export from the ER, and delivery via the Golgi complex to secretory granules for conversion to insulin and ultimate hormone storage. All of these steps are needed for generation and maintenance of the total insulin granule pool, and defects in any of these steps may, weakly or strongly, perturb glycemic control. The foregoing considerations have obvious potential relevance to the pathogenesis of type 2 diabetes and some forms of monogenic diabetes; conceivably, several of these concepts might also have implications for β cell failure in type 1 diabetes.

Preview pages

Reset
Next Page 0 Back

Continue reading with a subscription.

A subscription is required for you to read this article in full. If you are a subscriber, you may sign in to continue reading.

Already subscribed?

Click here to sign into your account.

Don't have a subscription?

Please select one of the subscription options, which includes a low-cost option just for this article.

At an institution or library?

If you are at an institution or library and believe you should have access, please check with your librarian or administrator (more information).

Problems?

Please try these troubleshooting tips.

  • Purchase this article
  • $10
  • Purchasing this article will give you full access for the calendar year.
  • Purchase article
  • Purchase Site Pass
  • $25
  • This will give you access to every article on the site for 24 hours.
  • Order site pass
  • Online subscription
  • $95
  • Individual online subscriptions give you full online access for the calendar year.
  • Individual online subscriptions ordered from September 1st on will receive access for the remainder of current year as well as for the full following year subscription term.
  • Order Online
  • JCI This Month subscription
  • $135
  • JCI This Month is a 16- to 20-page overview of the articles published each month
  • Subscribing to JCI This Month also gives subscribers full online access for the calendar year.
  • *Price outside U.S. and Canada: $195.
  • JCI This Month + Online
Advertisement