Secretion of Proinsulin C-Peptide by Pancreatic β Cells and its Circulation in Blood

Rubenstein, Arthur H.; Clark, Jeffrey L.; Melani, F; Steiner, Donald F.

doi:10.1038/224697a0

Cited by 301 publications

(150 citation statements)

References 11 publications

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“…r p .39 P p .0001 Fasting C-peptide was not measured in nondiabetic subjects; therefore, a comparison between AIR and IR C was not possible. However, given the equimolar relationship between insulin and C-peptide (Rubenstein et al 1969), we would expect the correlation to be similar.…”

Section: Empirical Metabolic Indicesmentioning

confidence: 99%

The Finland–United States Investigation of Non–Insulin‐Dependent Diabetes Mellitus Genetics (FUSION) Study. II. An Autosomal Genome Scan for Diabetes‐Related Quantitative‐Trait Loci

Watanabe¹,

Ghosh²,

Langefeld³

et al. 2000

Am. J Hum. Genet.

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Type 2 diabetes mellitus is a complex disorder encompassing multiple metabolic defects. We report results from an autosomal genome scan for type 2 diabetes-related quantitative traits in 580 Finnish families ascertained for an affected sibling pair and analyzed by the variance components-based quantitative-trait locus (QTL) linkage approach. We analyzed diabetic and nondiabetic subjects separately, because of the possible impact of disease on the traits of interest. In diabetic individuals, our strongest results were observed on chromosomes 3 (fasting Cpeptide/glucose: maximum LOD score [MLS] p 3.13 at 53.0 cM) and 13 (body-mass index: MLS p 3.28 at 5.0 cM). In nondiabetic individuals, the strongest results were observed on chromosomes 10 (acute insulin response: MLS p 3.11 at 21.0 cM), 13 (2-h insulin: MLS p 2.86 at 65.5 cM), and 17 (fasting insulin/glucose ratio: MLS p 3.20 at 9.0 cM). In several cases, there was evidence for overlapping signals between diabetic and nondiabetic individuals; therefore we performed joint analyses. In these joint analyses, we observed strong signals for chromosomes 3 (body-mass index: MLS p 3.43 at 59.5 cM), 17 (empirical insulin-resistance index: MLS p 3.61 at 0.0 cM), and 19 (empirical insulin-resistance index: MLS p 2.80 at 74.5 cM). Integrating genome-scan results from the companion article by Ghosh et al., we identify several regions that may harbor susceptibility genes for type 2 diabetes in the Finnish population.

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Section: Empirical Metabolic Indicesmentioning

confidence: 99%

The Finland–United States Investigation of Non–Insulin‐Dependent Diabetes Mellitus Genetics (FUSION) Study. II. An Autosomal Genome Scan for Diabetes‐Related Quantitative‐Trait Loci

Watanabe¹,

Ghosh²,

Langefeld³

et al. 2000

Am. J Hum. Genet.

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“…Insulin is the key hormone regulating intermediary metabolism; it coordinates the uptake and storage of glucose, and provides an integrated signal of energy balance to the brain (Norman and Litwack, 1997;Schwartz et al, 1992;Strack et al, 1995). When insulin is produced from proinsulin in the pancreas, the C-peptide molecule is cleaved off and released into the bloodstream on an equimolar basis (Melani et al, 1970;Rubenstein et al, 1969). Unlike insulin, C-peptide does not undergo significant clearance by the liver, meaning that it is probably a better indicator of pancreatic insulin secretion than circulating insulin itself (Polonsky et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

Urinary C-peptide tracks seasonal and individual variation in energy balance in wild chimpanzees

Thompson

Muller

Wrangham

et al. 2009

Hormones and Behavior

105

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C-peptide of insulin presents a promising new tool for behavioral ecologists that allows for regular, noninvasive assessment of energetic condition in wild animals. C-peptide is produced on an equimolar basis with insulin, thus is indicative of the body's response to available glucose and, with repeated measurement, provides a biomarker of energy balance. As yet, few studies have validated the efficacy of C-peptide for monitoring energy balance in wild animals. Here, we assess seasonal and interindividual variation in urinary C-peptide concentrations of East African chimpanzees (Pan troglodytes schweinfurthii). We assayed 519 urine samples from 13 adult male chimpanzees in the Kanyawara community of Kibale National Park, Uganda. Cpeptide levels were significantly predicted by the total amount of fruit and the amount of preferred fruit in the diet. However, chimpanzees had very low C-peptide titers during an epidemic of severe respiratory illness, despite highly favorable feeding conditions. Kanyawara males had significantly lower C-peptide levels than males at Ngogo, a nearby chimpanzee community occupying a more productive habitat. Among Kanyawara males, low-ranking males had consistently higher C-peptide levels than dominant males. While counterintuitive, this result supports previous findings of costs associated with dominance in male chimpanzees. Our preliminary investigations demonstrate that C-peptide has wide applications in field research, providing an accessible tool for evaluating seasonal and individual variation in energetic condition, as well as the costs of processes such as immune function and reproduction.

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“…It was fortunate that we had gone the extra mile of sequencing in addition to simply peptide mapping the bovine C-peptide, as we could be confident that both sequences were correct, and their identical structures also strongly supported the origin of the pancreatic C-peptide from proinsulin (24,26). Biosynthetic studies carried out by Jeffrey Clark and Arthur H. Rubenstein, who had joined my laboratory group in 1968, demonstrated that the molar ratio of insulin to C-peptide both within rat islets and in the medium after secretion was very close to unity, confirming that the C-peptide and insulin are stored together (in the secretory granules) after conversion and then co-secreted upon stimulation by glucose (27).…”

Section: Reflections: Adventures With Insulin In the Islets Of Langermentioning

confidence: 90%

Adventures with Insulin in the Islets of Langerhans

Steiner

2011

Journal of Biological Chemistry

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Insulin is a small but beautifully organized protein with a unique two-chain structure, the first protein to be sequenced. The mechanism of its biosynthesis invited much initial speculation but was finally clarified by the discovery of proinsulin, its single-chain precursor. The rich present-day field of protein precursor processing via post-translational proteolysis within the secretory pathway arose in the early 1970s as an offshoot of studies on insulin biosynthesis, which provided a novel paradigm for the generation of many other small neuroendocrine peptides. Before long, this mechanism was also found to play a role in the production of a much wider spectrum of proteins traversing the secretory pathway (receptors, growth factors, blood-clotting components, and even many viral envelope proteins) occurring in almost all eukaryotic cells. Indeed, yeast provided a key clue in the search for the proprotein convertases, the endoproteases that work along with carboxypeptidases and other modifying enzymes, such as the amidating enzyme complex (PAM), in converting inactive or less active precursor proteins into their fully active peptide products. In this "Reflections" article, I have tried to recount the people and events in my life that led to my involvement first in basic biochemical research and then on to insulin, proinsulin, and many relevant related areas that continue to fascinate and challenge my colleagues and me, as well as many other biomedical scientists today, as diabetes mellitus increasingly threatens human health throughout our contemporary world.

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Secretion of Proinsulin C-Peptide by Pancreatic β Cells and its Circulation in Blood

Cited by 301 publications

References 11 publications

The Finland–United States Investigation of Non–Insulin‐Dependent Diabetes Mellitus Genetics (FUSION) Study. II. An Autosomal Genome Scan for Diabetes‐Related Quantitative‐Trait Loci

The Finland–United States Investigation of Non–Insulin‐Dependent Diabetes Mellitus Genetics (FUSION) Study. II. An Autosomal Genome Scan for Diabetes‐Related Quantitative‐Trait Loci

Urinary C-peptide tracks seasonal and individual variation in energy balance in wild chimpanzees

Adventures with Insulin in the Islets of Langerhans

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