Proinsulin

A pancreatic polypeptide of about 110 amino acids, depending on the species, that is the precursor of insulin. Proinsulin, produced by the PANCREATIC BETA CELLS, is comprised sequentially of the N-terminal B-chain, the proteolytically removable connecting C-peptide, and the C-terminal A-chain. It also contains three disulfide bonds, two between A-chain and B-chain. After cleavage at two locations, insulin and C-peptide are the secreted products. Intact proinsulin with low bioactivity also is secreted in small amounts.

Networked: 1195 relevant articles (28 outcomes, 143 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Experts

1.	Arvan, Peter: 19 articles (01/2022 - 04/2005)
2.	Pfützner, Andreas: 18 articles (05/2020 - 01/2003)
3.	Weiss, Michael A: 14 articles (01/2022 - 01/2009)
4.	Haataja, Leena: 14 articles (11/2021 - 10/2013)
5.	Liu, Ming: 14 articles (09/2021 - 04/2005)
6.	Zethelius, Björn: 13 articles (11/2017 - 05/2002)
7.	Harrison, Leonard C: 13 articles (06/2013 - 01/2003)
8.	Forst, Thomas: 13 articles (05/2012 - 01/2003)
9.	Lind, Lars: 11 articles (11/2017 - 03/2003)
10.	Luo, Zhong-Cheng: 10 articles (01/2021 - 09/2010)

Related Diseases

1.	Insulin Resistance 01/01/2016 - "To study the characteristics of β-cell dysfunction and insulin resistance (IR) in the first-degree relatives (FDRs) of T2DM in Chinese population and to examine the usefulness of proinsulin (PI) for evaluating β-cell dysfunction. " 05/01/2015 - "The study showed that cell cycle regulating genes might have a distinctive effect on gestational insulin sensitivity, β-cell function and proinsulin conversion in pregnant Han Chinese women." 09/01/2007 - "The association between the risk alleles of the two SNPs studied and levels of proinsulin in plasma, identified when adjusting for insulin sensitivity using euglycaemic-hyperinsulinaemic clamp measurements in this study, is an important novel finding." 01/01/2022 - "Because in most mammalian cell lines even wild-type proinsulin exhibits limited folding efficiency, molecular barriers to folding uncovered by NCR MIDY mutations may pertain to β-cell dysfunction in non-syndromic type 2 DM due to INS-gene overexpression in the face of peripheral insulin resistance. " 11/01/2018 - "Further, our data demonstrate that whole-body insulin resistance is associated with underlying defects in proinsulin secretion, which become detectable only in the presence of increased insulin secretion demand."
2.	Type 1 Diabetes Mellitus (Autoimmune Diabetes) 01/01/1988 - "Under certain conditions, proinsulin might therefore prove effective in the long-term treatment of the insulin-dependent diabetes mellitus." 02/24/2006 - "In this study, we sought to elucidate the potential of HAC vectors carrying the human proinsulin transgene for gene therapy of insulin-dependent diabetes mellitus (IDDM) using non-beta-cells as a host for the vector. " 11/01/2021 - "Proinsulin production constitutes a major load on β-cell endoplasmic reticulum (ER), and decompensated ER stress is a cause of β-cell failure and loss in both type 1 diabetes (T1D) and T2D. " 01/01/2021 - "Proinsulin-Reactive CD4 T Cells in the Islets of Type 1 Diabetes Organ Donors." 01/01/2021 - "We also observed reduced colocalisation of proinsulin with LAMP1 in donors with type 1 diabetes (p < 0.001). "
3.	Type 2 Diabetes Mellitus (MODY) 01/01/2003 - "In short-term studies (<5 years), proinsulin predicts the development of Type 2 diabetes. " 12/01/2000 - "In the present study, multivariate analysis was performed to determine what factors contributed to the disproportionately elevated plasma proinsulin levels in Japanese patients with Type 2 diabetes (n=276). " 09/01/1998 - "In the San Antonio Study and in the Hoorn Study high fasting proinsulin levels, reflecting beta-cell dysfunction, were associated with progression to NIDDM. " 11/01/2023 - "proinsulin) are observed clinically in type 1 and type 2 diabetes. " 07/27/2023 - "Impaired redox homeostasis in the endoplasmic reticulum (ER) may contribute to proinsulin misfolding and thus to activate the unfolded protein response (UPR) and apoptotic pathways, culminating in pancreatic β-cell loss and type 2 diabetes (T2D). "
4.	Hyperglycemia 01/01/2023 - "These findings suggest that Cpe and proper proinsulin processing are critical in maintaining β-cell function during the development of hyperglycemia. " 01/01/2023 - "Synchronized proinsulin trafficking reveals delayed Golgi export accompanies β-cell secretory dysfunction in rodent models of hyperglycemia." 01/01/2016 - "We report the correction of hyperglycemia of STZ induced diabetic mice using one intravenous systemic administration of a single stranded serotype 8 pseudotyped adeno-associated virus (ssAAV2/8) vector encoding the human proinsulin gene under a constitutive liver specific promoter. " 08/01/2015 - "We previously showed that hyperglycemia induces the appearance of proinsulin (PI)-producing proinflammatory bone marrow (BM)-derived cells (PI-BMDCs) in rodents. " 10/01/2011 - "An increased proinsulin concentration may be a marker for mortality in ACS patients with hyperglycemia at admission and without known diabetes. "
5.	Chronic Kidney Failure (Chronic Renal Failure) 01/01/2015 - "This is the first reported case which characterizes the chronic elevation of proinsulin in a patient with ESRD, as well as its dramatic increase after a presumed solitary exposure to sulfonylurea. " 02/01/1984 - "The fasting levels of proinsulin in 29 patients with chronic renal failure (0.95 +/- 0.05) were significantly higher than those in 10 patients with liver cirrhosis (0.46 +/- 0.04), six with muscular dystrophy (0.37 +/- 0.02) and 52 normal subjects (0.24 +/- 0.02 ng/ml, mean +/- S.E.). " 01/01/2015 - "The 72-hour fast conducted gives insight into the clearance of insulin, proinsulin, and C-peptide after sulfonylurea ingestion in ESRD. " 02/01/1984 - "The insulin levels in liver cirrhosis and muscular dystrophy were significantly greater than those in normal subjects and increased molar ratios of proinsulin to total insulin immunoreactivity in chronic renal failure were observed. "

Related Drugs and Biologics

1.	Insulin (Novolin)
2.	C-Peptide
3.	Glucose (Dextrose)
4.	Adiponectin
5.	Peptides (Polypeptides)
6.	Interleukin 1 Receptor Antagonist Protein (Anakinra)
7.	Proteins (Proteins, Gene)
8.	Lipids
9.	Plasminogen Activator Inhibitor 1
10.	Pioglitazone (Actos)

Related Therapies and Procedures

1.	Therapeutics
2.	Glycemic Control
3.	Immunotherapy
4.	Pancreatectomy
5.	Secondary Prevention