We hypothesized that proinsulin expression in peripheral blood mononuclear cells is a process relevant to this condition and could represent a link among hyperglycemia, nerve susceptibility, and diabetic foot lesions.
We report a rare case of permanent neonatal diabetes (PND) due to insulin (INS) gene mutation in a 51-month-old girl who presented with hyperglycemia in the neonatal period.
Avoiding hyperglycemia in patients with EGI may be important for preventing excessive insulin demand indicated by disproportionately increased proinsulin secretion.
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 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.
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.
In addition, SMIT1 expression in INS-1E cells and isolated islets was augmented by acute high-glucose exposure and reduced in chronic hyperglycemia conditions.
Proinsulin levels remained within the normal range (suppressed with hypoglycemia) despite simultaneous almost unmeasurable C-peptide levels during hyperglycemia.
We hope to emphasize instead the homogeneity of nephropathy risk in both IDDM and NIDDM and also the idea that a common genetic susceptibility exists for all types of diabetes and is conditional on cumulative exposure to hyperglycemia.
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.
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.
We report the correction of hyperglycemia of STZ induced diabetic mice using one intravenous systemic administration of a single stranded serotype 8 pseudotyped adeno-associated virus (ssAAV2/8) vector encoding the human proinsulin gene under a constitutive liver specific promoter.
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.
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.
Hyperglycemia induced the expression of PKC-beta1 and PKC-beta2; however, only inhibition of PKC-beta1 but not PKC-beta2 led to a significant decrease of FGF-2 levels.
Apn has protective effects against hyperglycemia and can effectively enhance antioxidation, promote the secretion of insulin and reduce the accumulation of glycosylated products in T2DM mice; these effects were associated with inhibition of PKC and promotion of PKA signaling.
Taken together, our data suggest that hmunc13 serves as a diacylglycerol-activated, PKC-independent signaling pathway capable of inducing apoptosis and that this pathway may contribute to the renal cell complications of hyperglycemia.
We studied 86 adult offspring (mean age 40 years), 49 born to glucokinase mothers (exposed to hyperglycaemia in utero) and 37 born to glucokinase fathers (controls).