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: 750 relevant articles (11 outcomes, 98 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Experts

1.	Pfützner, Andreas: 13 articles (01/2015 - 01/2003)
2.	Forst, Thomas: 12 articles (05/2012 - 01/2003)
3.	Zethelius, Björn: 9 articles (03/2014 - 05/2002)
4.	Weiss, Michael A: 8 articles (08/2014 - 01/2009)
5.	Lind, Lars: 7 articles (03/2014 - 03/2003)
6.	Marx, Nikolaus: 7 articles (03/2013 - 03/2004)
7.	Maffioli, Pamela: 6 articles (07/2014 - 06/2010)
8.	Derosa, Giuseppe: 6 articles (07/2014 - 06/2010)
9.	Forst, T: 6 articles (06/2013 - 01/2005)
10.	Zethelius, B: 6 articles (01/2009 - 01/2000)

Related Diseases

1.	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." 05/01/2006 - "Anti-CD3 and nasal proinsulin combination therapy enhances remission from recent-onset autoimmune diabetes by inducing Tregs." 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. " 06/01/2014 - "Studying processing and presentation of proinsulin, which plays a pivotal role in autoimmune diabetes, we found that targeting to the ER has profound effects not only on how proinsulin is degraded, but also on regulation of its cellular levels. " 09/01/2013 - "The serum proinsulin level may be used as a parameter specifying the pathogenesis of type 1 diabetes mellitus."
2.	Hyperglycemia 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. " 01/01/2015 - "Hyperproinsulinemia is an indicator of β-cell dysfunction, and fasting proinsulin levels are elevated in patients with hyperglycemia. " 10/01/2011 - "An increased proinsulin concentration may be a marker for mortality in ACS patients with hyperglycemia at admission and without known diabetes. " 05/01/2011 - "Although there have been reports of hyperglycemia inducing proinsulin expression in extrapancreatic tissues, we did not observe bioluminescent signals from extrapancreatic tissues of diabetic MIP-TF mice. " 03/01/2009 - "Chronic hyperglycemia increases considerably the proinsulin secretion, overcrowding the ER. "
3.	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. "
4.	Insulin Resistance 06/01/2005 - "IRIS II study: intact proinsulin is confirmed as a highly specific indicator for insulin resistance in a large cross-sectional study design." 02/01/1999 - "Based on the results of their study the authors assume that examination of intact proinsulin is a valid "basal" indicator of insulin resistance. " 01/01/2015 - "Elevated fasting intact proinsulin is a biomarker of late-stage ß-cell-dysfunction associated with clinically relevant insulin resistance. " 02/01/2013 - "Proinsulin may represent a predictive marker for assessing insulin resistance and reduced β-cell function. " 05/01/2011 - "Insulin resistance (IR) and deterioration of beta-cell secretion are main features in the development of type 2 diabetes, which is reflected in increasing serum intact proinsulin levels in later disease stage. "
5.	Type 2 Diabetes Mellitus (MODY) 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. " 09/01/2015 - "The blood concentration of intact proinsulin, but not total proinsulin, has been suggested to be a diagnostic marker for type 2 diabetes mellitus (T2DM), but a sensitive assay specific for rodent intact proinsulin is lacking. " 01/01/2015 - "We aimed to examine the association between impaired proinsulin processing in pancreatic beta cells and type 2 diabetes mellitus in non-obese Japanese patients. " 01/01/2015 - "The association between impaired proinsulin processing and type 2 diabetes mellitus in non-obese Japanese individuals." 10/25/2013 - "Upon chronic up-regulation of proinsulin synthesis, misfolded proinsulin can accumulate in the endoplasmic reticulum (ER) of pancreatic β-cells, promoting ER stress and type 2 diabetes mellitus. "

Related Drugs and Biologics

1.	Insulin (Novolin)
2.	C-Peptide
3.	Glucose (Dextrose)
4.	DNA (Deoxyribonucleic Acid)
5.	Interleukin 1 Receptor Antagonist Protein (Anakinra)
6.	Glipizide (Glucotrol)
7.	Adiponectin
8.	Leptin
9.	Complementary DNA (cDNA)
10.	Plasminogen Activator Inhibitor 1

Related Therapies and Procedures

1.	Kidney Transplantation
2.	Cardiopulmonary Resuscitation (CPR)
3.	Transplantation (Transplant Recipients)
4.	Aftercare (After-Treatment)
5.	Pancreatectomy