Proinsulin levels remained within the normal range (suppressed with hypoglycemia) despite simultaneous almost unmeasurable C-peptide levels during hyperglycemia.
Accumulation of misfolded proinsulin beyond a certain threshold begins to interfere with the normal intracellular transport of bystander proinsulin, leading to diminished insulin production and hyperglycemia, as well as exacerbating ER stress.
Analysis of blood glucose in diabetic nude mice with transplanted cells showed that proinsulin production by these cells was strongly suppressed by GCV treatment in vivo as reflected by the reversal to hyperglycemia.
Avoiding hyperglycemia in patients with EGI may be important for preventing excessive insulin demand indicated by disproportionately increased proinsulin secretion.
In addition, SMIT1 expression in INS-1E cells and isolated islets was augmented by acute high-glucose exposure and reduced in chronic hyperglycemia conditions.
In every patient, fasting insulin, proinsulin, C-peptide and 1,5-anhydro-d-glucitol concentrations were assayed as markers of insulin secretion, peripheral resistance to insulin, and acute hyperglycaemia.
In this report we present a family with permanent neonatal diabetes, heterozygous for a novel INS gene missense mutation, p.A24V, manifested with marked hyperglycemia and ketoacidosis, unstable glycemic control, requiring insulin therapy, rapid progression of long-term complications and accompanying physical pathological signs and brain lesions.
Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood.
The aim of this study was to conduct an in-depth analysis of pathological changes in retinas from INS <sup>C94Y</sup> pigs exposed to hyperglycaemia for more than 2 years, representing a chronic diabetic condition.
These findings demonstrate that hyperglycemia induces metastasis, and C-peptide prevents the hyperglycemia-induced metastasis in the lungs of diabetic mice by inhibiting VEGF-induced TGase2 activation and subsequent vascular leakage.-Jeon, H.-Y., Lee, Y.-J., Kim, Y.-S., Kim, S.-Y., Han, E.-T., Park, W. S., Hong, S.-H., Kim, Y.-M., Ha, K.-S. Proinsulin C-peptide prevents hyperglycemia-induced vascular leakage and metastasis of melanoma cells in the lungs of diabetic mice.
These findings indicate that elevated proinsulin and proinsulin/insulin ratios are secondary to increased demands on beta-cell secretion induced by hyperglycemia and insulin resistance with no discernible influence of family history of diabetes.