C-peptide

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Contents

C-peptide [1]
C-Peptide.svg
Identifiers
3D model (JSmol)
ChemSpider
MeSH C-Peptide
PubChem CID
UNII
  • InChI=1S/C112H179N35O46/c1-51(2)32-66(144-104(184)63(21-29-92(170)171)137-85(161)46-127-99(179)59(16-23-72(114)148)134-87(163)49-131-111(191)95(55(9)10)146-106(186)62(18-25-74(116)150)135-86(162)47-129-103(183)70(36-94(174)175)145-105(185)64(22-30-93(172)173)136-84(160)45-124-98(178)58(113)15-27-90(166)167)102(182)126-41-80(156)119-38-77(153)122-50-89(165)147-31-13-14-71(147)110(190)130-44-81(157)132-56(11)96(176)123-39-78(154)121-43-83(159)140-68(34-53(5)6)108(188)141-60(17-24-73(115)149)100(180)128-48-88(164)139-67(33-52(3)4)107(187)133-57(12)97(177)143-69(35-54(7)8)109(189)142-61(20-28-91(168)169)101(181)125-40-79(155)118-37-76(152)120-42-82(158)138-65(112(192)193)19-26-75(117)151/h51-71,95H,13-50,113H2,1-12H3,(H2,114,148)(H2,115,149)(H2,116,150)(H2,117,151)(H,118,155)(H,119,156)(H,120,152)(H,121,154)(H,122,153)(H,123,176)(H,124,178)(H,125,181)(H,126,182)(H,127,179)(H,128,180)(H,129,183)(H,130,190)(H,131,191)(H,132,157)(H,133,187)(H,134,163)(H,135,162)(H,136,160)(H,137,161)(H,138,158)(H,139,164)(H,140,159)(H,141,188)(H,142,189)(H,143,177)(H,144,184)(H,145,185)(H,146,186)(H,166,167)(H,168,169)(H,170,171)(H,172,173)(H,174,175)(H,192,193)/t56-,57-,58-,59-,60-,61-,62-,63-,64-,65-,66-,67-,68-,69-,70-,71-,95-/m0/s1 X mark.svgN
    Key: XTUNIGNWBZZIPT-NTMYLOQBSA-N X mark.svgN
  • InChI=1/C112H179N35O46/c1-51(2)32-66(144-104(184)63(21-29-92(170)171)137-85(161)46-127-99(179)59(16-23-72(114)148)134-87(163)49-131-111(191)95(55(9)10)146-106(186)62(18-25-74(116)150)135-86(162)47-129-103(183)70(36-94(174)175)145-105(185)64(22-30-93(172)173)136-84(160)45-124-98(178)58(113)15-27-90(166)167)102(182)126-41-80(156)119-38-77(153)122-50-89(165)147-31-13-14-71(147)110(190)130-44-81(157)132-56(11)96(176)123-39-78(154)121-43-83(159)140-68(34-53(5)6)108(188)141-60(17-24-73(115)149)100(180)128-48-88(164)139-67(33-52(3)4)107(187)133-57(12)97(177)143-69(35-54(7)8)109(189)142-61(20-28-91(168)169)101(181)125-40-79(155)118-37-76(152)120-42-82(158)138-65(112(192)193)19-26-75(117)151/h51-71,95H,13-50,113H2,1-12H3,(H2,114,148)(H2,115,149)(H2,116,150)(H2,117,151)(H,118,155)(H,119,156)(H,120,152)(H,121,154)(H,122,153)(H,123,176)(H,124,178)(H,125,181)(H,126,182)(H,127,179)(H,128,180)(H,129,183)(H,130,190)(H,131,191)(H,132,157)(H,133,187)(H,134,163)(H,135,162)(H,136,160)(H,137,161)(H,138,158)(H,139,164)(H,140,159)(H,141,188)(H,142,189)(H,143,177)(H,144,184)(H,145,185)(H,146,186)(H,166,167)(H,168,169)(H,170,171)(H,172,173)(H,174,175)(H,192,193)/t56-,57-,58-,59-,60-,61-,62-,63-,64-,65-,66-,67-,68-,69-,70-,71-,95-/m0/s1
    Key: XTUNIGNWBZZIPT-NTMYLOQBBL
  • CC(C)CC(C(=O)NC(C)C(=O)NC(CC(C)C)C(=O)NC(CCC(=O)O)C(=O)NCC(=O)NCC(=O)NCC(=O)NC(CCC(=O)N)C(=O)O)NC(=O)CNC(=O)C(CCC(=O)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)CNC(=O)C(C)NC(=O)CNC(=O)C1CCCN1C(=O)CNC(=O)CNC(=O)CNC(=O)C(CC(C)C)NC(=O)C(CCC(=O)O)NC(=O)CNC(=O)C(CCC(=O)N)NC(=O)CNC(=O)C(C(C)C)NC(=O)C(CCC(=O)N)NC(=O)CNC(=O)C(CC(=O)O)NC(=O)C(CCC(=O)O)NC(=O)CNC(=O)C(CCC(=O)O)N
Properties
C129H211N35O48
Molar mass 3020.29 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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The connecting peptide, or C-peptide, is a short 31-amino-acid polypeptide that connects insulin's A-chain to its B-chain in the proinsulin molecule. In the context of diabetes or hypoglycemia, a measurement of C-peptide blood serum levels can be used to distinguish between different conditions with similar clinical features.

In the insulin synthesis pathway, first preproinsulin is translocated into the endoplasmic reticulum of beta cells of the pancreas with an A-chain, a C-peptide, a B-chain, and a signal sequence. The signal sequence is cleaved from the N-terminus of the peptide by a signal peptidase, leaving proinsulin. After proinsulin is packaged into vesicles in the Golgi apparatus (beta-granules), the C-peptide is removed, leaving the A-chain and B-chain bound together by disulfide bonds, that constitute the insulin molecule.

History

Proinsulin C-peptide was first described in 1967 in connection with the discovery of the insulin biosynthesis pathway. [2] Isolation of bovin C-peptide, determination of sequence, preparation of human C-peptide were done in 1971. [3] C-peptide serves as a linker between the A- and the B- chains of insulin and facilitates the efficient assembly, folding, and processing of insulin in the endoplasmic reticulum. Equimolar amounts of C-peptide and insulin are then stored in secretory granules of the pancreatic beta cells and both are eventually released to the portal circulation. Initially, the sole interest in C-peptide was as a marker of insulin secretion and has, as such, been of great value in furthering the understanding of the pathophysiology of type 1 and type 2 diabetes. The first documented use of the C-peptide test was in 1972. [4] In the first decade of 21st century, C-peptide has been found to be a bioactive peptide in its own right, with effects on microvascular blood flow and tissue health. [5]

Function

Cellular effects of C-peptide

C-peptide has been shown to bind to the surface of a number of cell types such as neuronal, endothelial, fibroblast and renal tubular, at nanomolar concentrations to a receptor that is likely G-protein-coupled. The signal activates Ca2+-dependent intracellular signaling pathways such as MAPK, PLCγ, and PKC, leading to upregulation of a range of transcription factors as well as eNOS and Na+K+ATPase activities. [6] The latter two enzymes are known to have reduced activities in patients with type I diabetes and have been implicated in the development of long-term complications of type I diabetes such as peripheral and autonomic neuropathy.

In vivo studies in animal models of type 1 diabetes have established that C-peptide administration results in significant improvements in nerve and kidney function. Thus, in animals with early signs of diabetes-induced neuropathy, C peptide treatment in replacement dosage results in improved peripheral nerve function, as evidenced by increased nerve conduction velocity, increased nerve Na+,K+ ATPase activity, and significant amelioration of nerve structural changes. [7] Likewise, C-peptide administration in animals that had C-peptide deficiency (type 1 model) with nephropathy improves renal function and structure; it decreases urinary albumin excretion and prevents or decreases diabetes-induced glomerular changes secondary to mesangial matrix expansion. [8] [9] [10] [11] C-peptide also has been reported to have anti-inflammatory effects as well as aid repair of smooth muscle cells. [12] [13] A recent epidemiologic study suggests a U-shaped relationship between C-peptide levels and risk of cardiovascular disease. [14]

Clinical uses of C-peptide testing

Patients with diabetes may have their C-peptide levels measured as a means of distinguishing type 1 diabetes from type 2 diabetes or maturity-onset diabetes of the young (MODY). [15] Measuring C-peptide can help to determine how much of their own natural insulin a person is producing as C-peptide is secreted in equimolar amounts to insulin. C-peptide levels are measured instead of insulin levels because C-peptide can assess a person's own insulin secretion even if they receive insulin injections, and because the liver metabolizes a large and variable amount of insulin secreted into the portal vein but does not metabolise C-peptide, meaning blood C-peptide may be a better measure of portal insulin secretion than insulin itself. [16] [17] A very low C-peptide confirms Type 1 diabetes and insulin dependence and is associated with high glucose variability, hyperglycaemia and increased complications. The test may be less sufficient to diagnose or recognize a subgroup of type 1 diabetes named Latent autoimmune diabetes in adults (LADA), whose C-peptide levels may not be as low as those in typical Type 1 diabetes while may sometimes overlap with those seen in type 2 diabetes, and Beta-cell antibody testing is needed for better diagnosis in this case. [18] [19]

C-peptide can be used for differential diagnosis of hypoglycemia. The test may be used to help determine the cause of hypoglycaemia (low glucose), values will be low if a person has taken an overdose of insulin but not suppressed if hypoglycaemia is due to an insulinoma or sulphonylureas.

Factitious (or factitial) hypoglycemia may occur secondary to the surreptitious use of insulin. Measuring C-peptide levels will help differentiate a healthy patient from a diabetic one.

C-peptide may be used for determining the possibility of gastrinomas associated with Multiple Endocrine Neoplasm syndromes (MEN 1). Since a significant number of gastrinomas are associated with MEN involving other hormone producing organs (pancreas, parathyroids, and pituitary), higher levels of C-peptide together with the presence of a gastrinoma suggest that organs besides the stomach may harbor neoplasms.

C-peptide levels may be checked in women with Polycystic Ovarian Syndrome (PCOS) to help determine degree of insulin resistance.

Ultrasensitive C-peptide assays have made it possible to detect very low levels of circulating C-peptide even in patients with longstanding type-1 diabetes. [20] Studies have demonstrated that the presence of residual C-peptide in longstanding type-1 diabetes is associated with a lower risk for developing microvascular complications and a significant reduction in incidence of severe hypoglycaemia. [21]

Therapeutics

Therapeutic use of C-peptide has been explored in small clinical trials in diabetic kidney disease. [22] [23] Creative Peptides, [24] Eli Lilly, [25] and Cebix [26] all had drug development programs for a C-peptide product. Cebix had the only ongoing program until it completed a Phase IIb trial in December 2014 that showed no difference between C-peptide and placebo, and it terminated its program and went out of business. [27] [28]

Related Research Articles

<span class="mw-page-title-main">Hypoglycemia</span> Decrease in blood sugar

Hypoglycemia, also spelled hypoglycaemia or hypoglycæmia, sometimes called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose below 70 mg/dL (3.9 mmol/L), symptoms associated with hypoglycemia, and resolution of symptoms when blood sugar returns to normal. Hypoglycemia may result in headache, tiredness, clumsiness, trouble talking, confusion, fast heart rate, sweating, shakiness, nervousness, hunger, loss of consciousness, seizures, or death. Symptoms typically come on quickly.

<span class="mw-page-title-main">Insulin</span> Peptide hormone

Insulin is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (INS) gene. It is the main anabolic hormone of the body. It regulates the metabolism of carbohydrates, fats, and protein by promoting the absorption of glucose from the blood into cells of the liver, fat, and skeletal muscles. In these tissues the absorbed glucose is converted into either glycogen, via glycogenesis, or fats (triglycerides), via lipogenesis; in the liver, glucose is converted into both. Glucose production and secretion by the liver are strongly inhibited by high concentrations of insulin in the blood. Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is thus an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules in the cells. Low insulin in the blood has the opposite effect, promoting widespread catabolism, especially of reserve body fat.

The following is a glossary of diabetes which explains terms connected with diabetes.

<span class="mw-page-title-main">Beta cell</span> Type of cell found in pancreatic islets

Beta cells (β-cells) are specialized endocrine cells located within the pancreatic islets of Langerhans responsible for the production and release of insulin and amylin. Constituting ~50–70% of cells in human islets, beta cells play a vital role in maintaining blood glucose levels. Problems with beta cells can lead to disorders such as diabetes.

<span class="mw-page-title-main">Proinsulin</span> Precursor protein in humans

Proinsulin is the prohormone precursor to insulin made in the beta cells of the Pancreatic Islets, specialized regions of the pancreas. In humans, proinsulin is encoded by the INS gene. The pancreatic islets only secrete between 1% and 3% of proinsulin intact. However, because proinsulin has a longer half life than insulin, it can account for anywhere from 5–30% of the insulin-like structures circulating in the blood. There are higher concentrations of proinsulin after meals and lower levels when a person is fasting. Additionally, while proinsulin and insulin have structural differences, proinsulin does demonstrate some affinity for the insulin receptor. Due to the relative similarities in structure, proinsulin can produce between 5% and 10% of the metabolic activity similarly induced by insulin.

Drugs used in diabetes treat diabetes mellitus by decreasing glucose levels in the blood. With the exception of insulin, most GLP-1 receptor agonists, and pramlintide, all diabetes medications are administered orally and are thus called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of hypoglycemic drugs, and selection of the appropriate agent depends on the nature of diabetes, age, and situation of the person, as well as other patient factors.

<span class="mw-page-title-main">Sulfonylurea</span> Class of organic compounds used in medicine and agriculture

Sulfonylureas or sulphonylureas are a class of organic compounds used in medicine and agriculture. The functional group consists of a sulfonyl group (-S(=O)2) with its sulphur atom bonded to a nitrogen atom of a ureylene group (N,N-dehydrourea, a dehydrogenated derivative of urea). The side chains R1 and R2 distinguish various sulfonylureas. Sulfonylureas are the most widely used herbicide.

<span class="mw-page-title-main">Insulinoma</span> Tumor of the pancreas which secretes insulin

An insulinoma is a tumour of the pancreas that is derived from beta cells and secretes insulin. It is a rare form of a neuroendocrine tumour. Most insulinomas are benign in that they grow exclusively at their origin within the pancreas, but a minority metastasize. Insulinomas are one of the functional pancreatic neuroendocrine tumour (PNET) group. In the Medical Subject Headings classification, insulinoma is the only subtype of "islet cell adenoma".

Hyperinsulinemic hypoglycemia describes the condition and effects of low blood glucose caused by excessive insulin. Hypoglycemia due to excess insulin is the most common type of serious hypoglycemia. It can be due to endogenous or injected insulin.

<span class="mw-page-title-main">Diabetic nephropathy</span> Chronic loss of kidney function

Diabetic nephropathy, also known as diabetic kidney disease, is the chronic loss of kidney function occurring in those with diabetes mellitus. Diabetic nephropathy is the leading causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD) globally. The triad of protein leaking into the urine, rising blood pressure with hypertension and then falling renal function is common to many forms of CKD. Protein loss in the urine due to damage of the glomeruli may become massive, and cause a low serum albumin with resulting generalized body swelling (edema) so called nephrotic syndrome. Likewise, the estimated glomerular filtration rate (eGFR) may progressively fall from a normal of over 90 ml/min/1.73m2 to less than 15, at which point the patient is said to have end-stage renal disease. It usually is slowly progressive over years.

<span class="mw-page-title-main">Amylin</span> Peptide hormone that plays a role in glycemic regulation

Amylin, or islet amyloid polypeptide (IAPP), is a 37-residue peptide hormone. It is co-secreted with insulin from the pancreatic β-cells in the ratio of approximately 100:1 (insulin:amylin). Amylin plays a role in glycemic regulation by slowing gastric emptying and promoting satiety, thereby preventing post-prandial spikes in blood glucose levels.

<span class="mw-page-title-main">Type 1 diabetes</span> Form of diabetes mellitus

Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that occurs when pancreatic are destroyed by the body's immune system. Insulin is a hormone required by the body to store and convert blood sugar into energy. T1D results in high blood sugar levels in the body prior to treatment. Common symptoms include frequent urination, increased thirst, increased hunger, weight loss, and other complications. Additional symptoms may include blurry vision, tiredness, and slow wound healing. While some cases take longer, symptoms usually appear within weeks or a few months.

The main goal of diabetes management is to keep blood glucose (BG) levels as normal as possible. If diabetes is not well controlled, further challenges to health may occur. People with diabetes can measure blood sugar by various methods, such as with a BG meter or a continuous glucose monitor, which monitors over several days. Glucose can also be measured by analysis of a routine blood sample. Usually, people are recommended to control diet, exercise, and maintain a healthy weight, although some people may need medications to control their blood sugar levels. Other goals of diabetes management are to prevent or treat complications that can result from the disease itself and from its treatment.

<span class="mw-page-title-main">Glucagon-like peptide-1</span> Gastrointestinal peptide hormone involved in glucose homeostasis

Glucagon-like peptide-1 (GLP-1) is a 30- or 31-amino-acid-long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and certain neurons within the nucleus of the solitary tract in the brainstem upon food consumption. The initial product GLP-1 (1–37) is susceptible to amidation and proteolytic cleavage, which gives rise to the two truncated and equipotent biologically active forms, GLP-1 (7–36) amide and GLP-1 (7–37). Active GLP-1 protein secondary structure includes two α-helices from amino acid position 13–20 and 24–35 separated by a linker region.

<span class="mw-page-title-main">Blood sugar regulation</span> Hormones regulating blood sugar levels

Blood sugar regulation is the process by which the levels of blood sugar, the common name for glucose dissolved in blood plasma, are maintained by the body within a narrow range.

Complications of diabetes are secondary diseases that are a result of elevated blood glucose levels that occur in diabetic patients. These complications can be divided into two types: acute and chronic. Acute complications are complications that develop rapidly and can be exemplified as diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar state (HHS), lactic acidosis (LA), and hypoglycemia. Chronic complications develop over time and are generally classified in two categories: microvascular and macrovascular. Microvascular complications include neuropathy, nephropathy, and retinopathy; while cardiovascular disease, stroke, and peripheral vascular disease are included in the macrovascular complications.

Gliflozins are a class of drugs in the treatment of type 2 diabetes (T2D). They act by inhibiting sodium/glucose cotransporter 2 (SGLT-2), and are therefore also called SGLT-2 inhibitors. The efficacy of the drug is dependent on renal excretion and prevents glucose from going into blood circulation by promoting glucosuria. The mechanism of action is insulin independent.

<span class="mw-page-title-main">Glomerular hyperfiltration</span> Medical condition

Glomerular hyperfiltration is a situation where the filtration elements in the kidneys called glomeruli produce excessive amounts of pro-urine. It can be part of a number of medical conditions particularly diabetic nephropathy.

SGLT2 inhibitors are a class of medications that inhibit sodium-glucose transport proteins in the nephron, unlike SGLT1 inhibitors that perform a similar function in the intestinal mucosa. The foremost metabolic effect of this is to inhibit reabsorption of glucose in the kidney and therefore lower blood sugar. They act by inhibiting sodium/glucose cotransporter 2 (SGLT2). SGLT2 inhibitors are used in the treatment of type 2 diabetes. Apart from blood sugar control, gliflozins have been shown to provide significant cardiovascular benefit in people with type 2 diabetes. As of 2014, several medications of this class had been approved or were under development. In studies on canagliflozin, a member of this class, the medication was found to enhance blood sugar control as well as reduce body weight and systolic and diastolic blood pressure.

References

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  2. ↑ Steiner DF, Cunningham D, Spigelman L, Aten B (August 1967). "Insulin biosynthesis: evidence for a precursor". Science. 157 (3789): 697–700. Bibcode:1967Sci...157..697S. doi:10.1126/science.157.3789.697. PMID   4291105. S2CID   29382220.
  3. ↑ Brandenburg D (2008). "History and Diagnostic Significance of C-Peptide". Experimental Diabetes Research. 2008: 576862. doi: 10.1155/2008/576862 . ISSN   1687-5214. PMC   2396242 . PMID   18509495.
  4. ↑ Brandenburg D (2008). "History and diagnostic significance of C-peptide". Exp Diabetes Res. 2008: 576862. doi: 10.1155/2008/576862 . PMC   2396242 . PMID   18509495.
  5. ↑ Forst T, Weber MM, Kunt T, Pfützner A (2012). "Role of C-Peptide in the Regulation of Microvascular Blood Flow". Diabetes & C-Peptide. pp. 45–54. doi:10.1007/978-1-61779-391-2_5. ISBN   978-1-61779-390-5. Archived from the original on March 16, 2024. Retrieved March 15, 2024.
  6. ↑ Hills CE, Brunskill NJ (2008). "Intracellular signalling by C-peptide". Experimental Diabetes Research. 2008: 635158. doi: 10.1155/2008/635158 . PMC   2276616 . PMID   18382618.
  7. ↑ Sima AA, Zhang W, Sugimoto K, Henry D, Li Z, Wahren J, Grunberger G (July 2001). "C-peptide prevents and improves chronic Type I diabetic polyneuropathy in the BB/Wor rat". Diabetologia. 44 (7): 889–97. doi: 10.1007/s001250100570 . PMID   11508275.
  8. ↑ Samnegård B, Jacobson SH, Jaremko G, Johansson BL, Sjöquist M (October 2001). "Effects of C-peptide on glomerular and renal size and renal function in diabetic rats". Kidney International. 60 (4): 1258–65. doi: 10.1046/j.1523-1755.2001.00964.x . PMID   11576340.
  9. ↑ Samnegård B, Jacobson SH, Jaremko G, Johansson BL, Ekberg K, Isaksson B, et al. (March 2005). "C-peptide prevents glomerular hypertrophy and mesangial matrix expansion in diabetic rats". Nephrology, Dialysis, Transplantation. 20 (3): 532–8. doi:10.1093/ndt/gfh683. PMID   15665028.
  10. ↑ Nordquist L, Brown R, Fasching A, Persson P, Palm F (November 2009). "Proinsulin C-peptide reduces diabetes-induced glomerular hyperfiltration via efferent arteriole dilation and inhibition of tubular sodium reabsorption". American Journal of Physiology. Renal Physiology. 297 (5): F1265-72. doi:10.1152/ajprenal.00228.2009. PMC   2781335 . PMID   19741019.
  11. ↑ Nordquist L, Wahren J (2009). "C-Peptide: the missing link in diabetic nephropathy?". The Review of Diabetic Studies. 6 (3): 203–10. doi:10.1900/RDS.2009.6.203 (inactive November 1, 2024). PMC   2827272 . PMID   20039009.{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link)
  12. ↑ Luppi P, Cifarelli V, Tse H, Piganelli J, Trucco M (August 2008). "Human C-peptide antagonises high glucose-induced endothelial dysfunction through the nuclear factor-kappaB pathway". Diabetologia. 51 (8): 1534–43. doi: 10.1007/s00125-008-1032-x . PMID   18493738.
  13. ↑ Mughal RS, Scragg JL, Lister P, Warburton P, Riches K, O'Regan DJ, et al. (August 2010). "Cellular mechanisms by which proinsulin C-peptide prevents insulin-induced neointima formation in human saphenous vein". Diabetologia. 53 (8): 1761–71. doi:10.1007/s00125-010-1736-6. PMC   2892072 . PMID   20461358.
  14. ↑ Koska J, Nuyujukian DS, Bahn G, Zhou JJ, Reaven PD (2021). "Association of low fasting C-peptide levels with cardiovascular risk, visit-to-visit glucose variation and severe hypoglycemia in the Veterans Affairs Diabetes Trial (VADT)". Cardiovascular Diabetology. 20 (1): 232. doi: 10.1186/s12933-021-01418-z . PMC   8656002 . PMID   34879878.
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  16. ↑ Clark PM (September 1999). "Assays for insulin, proinsulin(s) and C-peptide". Annals of Clinical Biochemistry. 36 (5): 541–64. doi:10.1177/000456329903600501. PMID   10505204. S2CID   32483378.
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  18. ↑ R C, Udayabhaskaran V, Binoy J Paul, K.P Ramamoorthy (July 2013). "A study of non-obese diabetes mellitus in adults in a tertiary care hospital in Kerala, India". International Journal of Diabetes in Developing Countries. 33 (2): 83–85. doi:10.1007/s13410-013-0113-7. S2CID   71767996.
  19. ↑ O'Neal KS, Johnson JL, Panak RL (November 1, 2016). "Recognizing and Appropriately Treating Latent Autoimmune Diabetes in Adults". Diabetes Spectrum. 29 (4): 249–252. doi:10.2337/ds15-0047. PMC   5111528 . PMID   27899877. Archived from the original on March 15, 2024. Retrieved March 15, 2024.
  20. ↑ Keenan HA, Sun JK, Levine J, Doria A, Aiello LP, Eisenbarth G, Bonner-Weir S, King GL (August 10, 2010). "Residual Insulin Production and Pancreatic β-Cell Turnover After 50 Years of Diabetes: Joslin Medalist Study". Diabetes. 59 (11): 2846–2853. doi:10.2337/db10-0676. ISSN   0012-1797. PMC   2963543 . PMID   20699420. Archived from the original on March 16, 2024. Retrieved June 8, 2023.
  21. ↑ Jeyam A, Colhoun H, McGurnaghan S, Blackbourn L, McDonald TJ, Palmer CN, McKnight JA, Strachan MW, Patrick AW, Chalmers J, Lindsay RS, Petrie JR, Thekkepat S, Collier A, MacRury S (February 5, 2021). "Erratum. Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications. Diabetes Care 2021;44:390–398". Diabetes Care: dc21er04b. doi:10.2337/dc21er04b. ISSN   0149-5992. PMID   33547206. S2CID   237216616. Archived from the original on March 16, 2024. Retrieved June 8, 2023.
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  23. ↑ Shaw JA, Shetty P, Burns KD, Fergusson D, Knoll GA (2015). "C-peptide as a Therapy for Kidney Disease: A Systematic Review and Meta-Analysis". PLOS ONE. 10 (5): e0127439. Bibcode:2015PLoSO..1027439S. doi: 10.1371/journal.pone.0127439 . PMC   4439165 . PMID   25993479.
  24. ↑ "C-peptide - Creative Peptides -". AdisInsight. Archived from the original on September 13, 2018. Retrieved October 22, 2016.
  25. ↑ "C-peptide - Eli Lilly". AdisInsight. Archived from the original on September 12, 2018. Retrieved October 22, 2016.
  26. ↑ "C-peptide long-acting - Cebix". adisinsight.springer.com. AdisInsight. Archived from the original on November 16, 2018. Retrieved October 22, 2016.
  27. ↑ Bigelow BV (February 23, 2015). "Cebix Shuts Down Following Mid-Stage Trial of C-Peptide Drug". Xconomy. Archived from the original on December 28, 2018. Retrieved October 22, 2016.
  28. ↑ Garde D (February 24, 2015). "Cebix hangs it up after raising $50M for diabetes drug". FierceBiotech. Archived from the original on September 13, 2018. Retrieved October 22, 2016.
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