Effect of tetanus toxin on the accumulation of the permeant lipophilic cation tetraphenylphosphonium by guinea pig brain synaptosomes

Accumulation of the permeant lipophilic cation [(3)H]tetraphenylphosphonium (TPP(+)) by synaptosome preparations from guinea pig brain cerebral cortex is inhibited 1:10 by medium containing 193 mM K(+) and by veratridine. A further 1:10 to 1:15 decrease in TPP(+) uptake occurs under nitrogen and in the presence of mitochondrial inhibitors such as oligomycin, whereas starvation and succinate supplementation have no effect. These data indicate that, in analogy to intact neurons, there is an electrical potential (DeltaPsi, interior negative) of -60 to -80 mV across the synaptosomal membrane that is due primarily to a K(+) diffusion gradient (K(+) (in)-->K(+) (out)). The data also indicate that mitochondria entrapped within the synaptosome but not free mitochondria make a large contribution to the TPP(+) concentration gradients observed.Conditions are defined in which tetanus toxin binds specifically and immediately to synaptosomes in media used to measure TPP(+) uptake. Under these conditions tetanus toxin induces dose-dependent changes in TPP(+) uptake that are blocked by antitoxin and not mimicked by biologically inactivated toxin preparations. The effect of tetanus toxin on TPP(+) uptake is not evident in the presence of 193 mM K(+) or veratridine but remains under conditions known to abolish the mitochondrial DeltaPsi. Moreover, tetanus toxin has no effect on TPP(+) uptake by isolated synaptosomal mitochondria. The results thus define an in vitro action of tetanus toxin on the synaptosomal membrane that can be correlated with biological potency in vivo and is consistent with the in vivo effects of tetanus toxin on neuronal transmission.     

Dipeptidyl peptidase-4 expression in pancreatic tissue from patients with congenital hyperinsulinism

Congenital hyperinsulinism (CHI) is caused by unregulated insulin release and leads to hyperinsulinaemic-hypoglycaemia (HH). Glucagon like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), peptide YY (PYY) and the enzyme; dipeptidyl peptidase-4 (DPP-4) all regulate appetite and glucose homeostasis. These proteins have been identified as possible contributors to HH but the mechanism remains poorly understood. We aimed to look at the expression pattern of pancreatic DPP-4 in children with focal and diffuse CHI (FCHI and DCHI, respectively). Using immunohistochemistry; we determined DPP-4 expression patterns in the pancreas of CHI patients. DPP-4 was found to be expressed in the pancreatic β, α and δ-cells in and around the focal area. However, it was predominantly co-localised with β-cells in the paediatric tissue samples. Additionally, proliferating β-cells expressed DPP-4 in DCHI, which was absent in the FCHI pancreas. Insulin was found to be present in the exocrine acini and duct cells of the DCHI pancreas suggestive of exocrine to endocrine transdifferentiation. Furthermore, 6 medically-unresponsive DCHI pancreatic samples showed an up-regulation of total pancreatic DPP-4 expression. In conclusion; the expression studies have shown DPP-4 to be altered in HH, however, further work is required to understand the underlying role for this enzyme.     

Impact of a Community Health Workers–Led Structured Program on Blood Glucose Control Among Latinos With Type 2 Diabetes: The DIALBEST Trial

OBJECTIVE

Latinos with type 2 diabetes (T2D) face major healthcare access and disease management disparities. We examined the impact of the Diabetes Among Latinos Best Practices Trial (DIALBEST), a community health worker (CHW)–led structured intervention for improving glycemic control among Latinos with T2D.

RESEARCH DESIGN AND METHODS

A total of 211 adult Latinos with poorly controlled T2D were randomly assigned to a standard of healthcare (n = 106) or CHW (n = 105) group. The CHW intervention comprised 17 individual sessions delivered at home by CHWs over a 12-month period. Sessions addressed T2D complications, healthy lifestyles, nutrition, healthy food choices and diet for diabetes, blood glucose self-monitoring, and medication adherence. Demographic, socioeconomic, lifestyle, anthropometric, and biomarker (HbA_1c, fasting blood glucose, and lipid profile) data were collected at baseline and 3, 6, 12, and 18 months (6 months postintervention). Groups were equivalent at baseline.

RESULTS

Participants had high HbA_1c at baseline (mean 9.58% [81.2 mmol/mol]). Relative to participants in the control group, CHWs had a positive impact on net HbA_1c improvements at 3 months (−0.42% [−4.62 mmol/mol]), 6 months (−0.47% [−5.10 mmol/mol]), 12 months (−0.57% [−6.18 mmol/mol]), and 18 months (−0.55% [−6.01 mmol/mol]). The overall repeated-measures group effect was statistically significant (mean difference −0.51% [−5.57 mmol/mol], 95% CI −0.83, −0.19% [−9.11, −2.03 mmol/mol], P = 0.002). CHWs had an overall significant effect on fasting glucose concentration that was more pronounced at the 12- and 18-month visits. There was no significant effect on blood lipid levels, hypertension, and weight.

CONCLUSIONS

DIALBEST is an effective intervention for improving blood glucose control among Latinos with T2D.