C-Peptide replacement therapy in type 1 diabetes: are we in the trough of disillusionment?

Pinger, Cody; Entwistle, K.; Bell, Thomas M.; Liu, Y.; Spence, Dana M.

doi:10.1039/c7mb00199a

Cited by 18 publications

(14 citation statements)

References 42 publications

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“…The secretory capacity of DAA+ children with metabolic markers of carbohydrate metabolism disorders were saved, but there is a tendency for their decline. Conversely, the results of our studies on the C-peptide content day before the debut and in the disease manifestation, make the fact indisputable and coincide with the data of other authors affirming that significantly reduced the C-peptide level -the result of prolonged autoimmune aggression aggression in time, which is ending allowing us to use the study of C-peptide level together with DAA, as a hormonal marker of T1D development in children and adolescents [21,36].…”

Section: оригінальні дослідженняsupporting

confidence: 87%

Алгоритм Доклинической Диагностики Сахарного Диабета 1-Го Типа Как Основа Для Создания Реестра ДААт-Позитивных Детей И Подростков Украины С Прогнозированным Развитием Заболевания

Тronko¹,

Zak²,

Popova³

2019

Endokr.

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Aim — The establishment of mechanisms for T1D development at early and late preclinical stages of disease formation in children and adolescents. Material and methods. At the State Institution «V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine» mentioned the Program «Immunity in the preclinical period of T1D development» was initiated, on the basis of which the Register of marker-positive children with predictable development of type 1 diabetes was created, which includes 612 children aged from 7 to 15 years with burdened heredity, in which the titer of diabetes-associated autobodies (DAA), cytokines, levels of basal and postprandial glycemia and secretion of C-peptide at preclinical and clinical stages of T1D development in children and adolescents based on the performed clinical and immunological study. Results. The new data have been obtained at the State Institution «V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine», which allowed to substantially supplement the existing ideas about the type 1 diabetes (T1D) pathogenesis. As a result of the performed study, a group of marker-positive children with burdened heredity and a predicted risk of developing the disease was formed. It was found that an increased titer of DAA was observed in 162 (35.45%) of 457 children with burdened heredity with no less than two times determination of DAA presence in them, mainly GADA and IA‑2A, the clinical debut was manifested in 86 (53.08%) of them from 6 months to 16 years (27.4±4.3 months). The formula of combined occurrence and values of simultaneously increased DAA titers to islet autoantigens, namely IA‑2A + GADA, was determined, which is a predictor of both the duration of preclinical stage of T1D development and the debut rate. Impaired cytokine production (increase of the level of proinflammatory cytokines IL‑1α, IL‑6 and TNFα, IL‑8 and IL‑16 while reducing the concentration of IL‑4 in the PB) as key factors of the T1D pathogenesis, which determine the rate of T1D debut, and the aggressiveness of its course were also established. It was found that the early preclinical period of T1D development in DAA+ children was characterized by the presence of dysglycemia in the form of increased glycemia in 2 hour after the glucose tolerance test and a slight decrease in secretion of stimulated C-peptide; in addition, dysglycemia in the form of impaired fasting glycemia was added in DAA+children in the late preclinical period, and a decrease in both basal and stimulated secretion of the C-peptide was determined, indicating that the potential of pancreatic beta cells was depleted.

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Section: оригінальні дослідженняsupporting

confidence: 87%

Алгоритм Доклинической Диагностики Сахарного Диабета 1-Го Типа Как Основа Для Создания Реестра ДААт-Позитивных Детей И Подростков Украины С Прогнозированным Развитием Заболевания

Тronko¹,

Zak²,

Popova³

2019

Endokr.

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“…4 Islet xenotransplantation is becoming a clinical reality for DM therapy. 5 Postprandial glucose control, 6 C-peptide replacement 7 and phytomedicines intervention 8 have been explored for curing DM. Although these therapeutic approaches could alleviate the afflictions of patients with DM, they are unable to thoroughly cure DM.…”

Section: Introductionmentioning

confidence: 99%

Selenium-coated nanostructured lipid carriers used for oral delivery of berberine to accomplish a synergic hypoglycemic effect

Yin¹,

Hou²,

Yin³

et al. 2017

IJN

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Diabetes mellitus is an incurable metabolic disorder that seriously threatens human health. At present, there is no effective medication available to defeat it. This work intended to develop selenium-coated nanostructured lipid carriers (SeNLCs) for enhancing the oral bioavailability and the curative effect of berberine, an antidiabetic phytomedicine. Berberine-loaded SeNLCs (BB-SeNLCs) were prepared by hot-melt dispersion/homogenization procedure followed by in situ reduction. BB-SeNLCs were characterized by particle size, morphology, entrapment efficiency (EE) and in vitro release. Pharmacokinetics of berberine solution, berberine-loaded NLCs (BB-NLCs) and BB-SeNLCs were studied in Sprague Dawley rats administered by oral gavage. The prepared BB-SeNLCs were around 160 nm in particle size with an EE of 90%. In addition, BB-SeNLCs exhibited a better sustained release of berberine compared to the plain NLCs. After oral administration, BB-SeNLCs greatly enhanced the oral bioavailability of berberine, which was approximately 6.63 times as much as that of berberine solution. The hypoglycemic effect of BB-SeNLCs was also significantly superior to that of BB-NLCs and berberine solution. It turned out that sustained drug release and good intestinal absorption, plus the synergy of selenium, were basically responsible for enhanced oral bioavailability and hypoglycemic effect. Our findings show that SeNLCs are promising nanocarriers for oral delivery of berberine to strengthen the antidiabetic action.

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“…In addition, C‐peptide infusion increases the hyperemic myocardial blood flow and left‐ventricular function in T1DM patients . These data suggest that C‐peptide replacement therapy might play a role in preventing and potentially reverse some of the chronic diabetes complication, especially due to its ability to improve blood flow, in this group . However, the atheroprotective role of C‐peptide in T1DM patients remains unclear, and further studies in animal models and humans are thus warranted.…”

Section: Resultsmentioning

confidence: 98%

“…99 These data suggest that C-peptide replacement therapy might play a role in preventing and potentially reverse some of the chronic diabetes complication, especially due to its ability to improve blood flow, in this group. 100 However, the atheroprotective role of C-peptide in T1DM patients remains unclear, and further studies in animal models and humans are thus warranted. In the same way, the proatherogenic role of C-peptide in T2DM patients has not been well investigated.…”

Section: Figurementioning

confidence: 99%

The dual effect of C‐peptide on cellular activation and atherosclerosis: Protective or not?

Alves

Ortiz

Reis

et al. 2018

Diabetes Metabolism Res

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C-peptide is a cleavage product of proinsulin that acts on different type of cells, such as blood and endothelial cells. C-peptide biological effects may be different in type 1 and type 2 diabetes. Besides, there are further evidence for a functional interaction between C-peptide and insulin. In this way, C-peptide has ambiguous effects, acting as an antithrombotic or thrombotic molecule, depending on the physiological environment and disease conditions. Moreover, C-peptide regulates interaction of leucocytes, erythrocytes, and platelets with the endothelium. The beneficial effects include stimulation of nitric oxide production with its subsequent release by platelets and endothelium, the interaction with erythrocytes leading to the generation of adenosine triphosphate, and inhibition of atherogenic cytokine release. The undesirable action of C-peptide includes the chemotaxis of monocytes, lymphocytes, and smooth muscle cells. Also, C-peptide was related with increased lipid deposits and elevated smooth muscle cells proliferation in the vessel wall, contributing to atherosclerosis. Purpose of this review is to explore these dual roles of C-peptide on the blood, contributing at one side to haemostasis and the other to atherosclerotic process.

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C-Peptide replacement therapy in type 1 diabetes: are we in the trough of disillusionment?

Cited by 18 publications

References 42 publications

Selenium-coated nanostructured lipid carriers used for oral delivery of berberine to accomplish a synergic hypoglycemic effect

The dual effect of C‐peptide on cellular activation and atherosclerosis: Protective or not?

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