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The Pathobiology of Diabetes Mellitus

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Pancreatic Islet Biology

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

Abstract

Diabetes mellitus is an increasingly common condition characterized by hyperglycemia caused by varying degrees of destruction and/or dysfunction of the pancreatic islets causing complete or near-complete loss (as in type 1 diabetes) or insufficient (as in type 2 diabetes) insulin secretion. The hyperglycemia, with the related disturbances of carbohydrate, protein and lipid metabolism, contributes to extrapancreatic tissue damage, including poor wound healing and the long-term complications of diabetic retinopathy, nephropathy, neuropathy and accelerated atherosclerosis. While diabetes has been known since 2500 BC, the survival and long-term prognosis of people with type 1 diabetes have only started to improve recently. Key developments have been the availability of exogenous insulin injections (since 1922), self-blood glucose monitoring and improved insulin preparations and delivery methods (over the last 30 years) and, for a very small minority, pancreas or islet transplantation. While the pathophysiology of the hyperglycemia of type 2 diabetes and gestational diabetes is complex, failure of insulin secretion to fully compensate for insulin resistance underscores the importance of pancreatic islet dysfunction in this heterogeneous condition. In this chapter, we describe normal pancreas function and how it is disturbed and treated in the common forms of diabetes. We also describe the short- and long-term consequences of diabetes that stem from pancreatic islet failure. Current and emerging glucose control treatments, most of which are closely related to and derived from normal islet function, are also reviewed. We hope this chapter, complemented by others in this volume, will increase the reader’s interest in and understanding of pancreatic islet biology and the clinical and research challenges, and assist them in diabetes-related research to provide better clinical outcomes for those with or at risk of diabetes.

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Abbreviations

ACE:

Angiotensin-converting enzyme

ADA:

American Diabetes Association

AGEs:

Advanced glycation end-products

ACTH:

Adrenocorticotropic hormone

ADP:

Adenosine diphosphate

ATP:

Adenosine triphosphate

CCK:

Cholecystokinin

CGM:

Continuous glucose monitoring

CKD:

Chronic kidney disease

CRF:

Corticotropin-releasing factor (or hormone)

DCCT:

Diabetes control and complications trial

DNA:

Deoxyribonucleic acid

DIDMOAD:

Diabetes insipidus, diabetes mellitus, optic atrophy, deafness

DKA:

Diabetic ketoacidosis

DPP-4:

Dipeptidyl peptidase-4

EGP:

Endogenous glucose production

EDIC:

Epidemiology of diabetes interventions and complications

GFR:

Glomerular filtration rate

GH:

Growth hormone

GHRF:

Growth hormone-releasing factor

GHIH:

Growth hormone inhibitory hormone

GIP-1:

Glucose-dependent insulinotropic polypeptide-1

GLP-1:

Glucagon-like peptide-1

GLUT:

Glucose transporter

GSIS:

Glucose-stimulated insulin secretion

GTP:

Guanosine triphosphate

HIF:

Hypoxia inducible factor

IAPP:

Islet amyloid polypeptide

IV:

Intravenous

LADA:

Latent autoimmune diabetes of adulthood

MODY:

Maturity-onset diabetes of the young

mRNA:

Messenger ribonucleic acid

NADPH:

Nicotinamide adenine dinucleotide phosphate

oGTT:

Oral glucose tolerance test

PKC:

Protein kinase C

PP:

Pancreatic polypeptide

RER:

Rough endoplasmic reticulum

RRP:

Readily releasable pool

SD:

Standard deviation

T1D:

Type 1 diabetes mellitus

T2D:

Type 2 diabetes mellitus

TNF:

Tumor necrosis factor

TSH:

Thyroid-stimulating hormone

UKPDS:

United Kingdom Prospective Diabetes Study

VEGF:

Vascular endothelial growth factor

VIP:

Vasoactive intestinal peptide

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Acknowledgments

Authors are grateful for funding support from the University of Sydney, Sydney Medical School Foundation, and to Associate Professor Anand Hardikar and Dr. Mugdha Joglekar for helpful discussions.

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Authors and Affiliations

  1. NHMRC Clinical Trials Centre, University of Sydney, 92-94 Parramatta Rd, Camperdown, Sydney, 2050, Australia

    Alicia J. Jenkins, David N. O’Neal & Andrzej S. Januszewski

  2. Centre for Experimental Medicine, Queens University, Belfast, Northern Ireland, UK

    Alicia J. Jenkins

  3. Department of Endocrinology, St Vincent’s Hospital, Melbourne, Australia

    Alicia J. Jenkins, David N. O’Neal & Andrzej S. Januszewski

  4. Department of Diabetes and Endocrinology, The Canberra Hospital and the Australian National University Medical School, Canberra, Australia

    Christopher J. Nolan

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  1. Alicia J. Jenkins
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  2. David N. O’Neal
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  3. Christopher J. Nolan
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  4. Andrzej S. Januszewski
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Corresponding author

Correspondence to Alicia J. Jenkins .

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Editors and Affiliations

  1. NHMRC Clinical Trials Centre Diabetes and Islet-biology Group, The University of Sydney Faculty of Medicine, Sydney, New South Wales, Australia

    Anandwardhan A. Hardikar

Additional information

This chapter is dedicated to Marie-Elise and Liam McCallum and to other people who live with type 1 diabetes, with the hope that results of ongoing and future medical research will lessen the impact of diabetes on their lives.

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Jenkins, A.J., O’Neal, D.N., Nolan, C.J., Januszewski, A.S. (2016). The Pathobiology of Diabetes Mellitus. In: A. Hardikar, A. (eds) Pancreatic Islet Biology. Stem Cell Biology and Regenerative Medicine. Springer, Cham. https://doi.org/10.1007/978-3-319-45307-1_1

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