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Purpose: External fixator pin site overlap with definitive fixation implants (pin-plate overlap) has been identified as a risk factor for surgical site infection in tibial plateau fractures. Despite this, pin-plate overlap occurs in 24–38% of patients. This study sought to identify radiographic characteristics associated with pin-plate overlap to help minimize occurrences. Methods: 283 patients at two Level I trauma centers were retrospectively reviewed. Radiographic measurements were recorded including fracture length, distance from fracture to proximal tibial pin site, and pin site distance-to-fracture (PSF) ratio. Results: 70 (24.7%) cases of pin-plate overlap were identified. Pin-plate overlap was associated with increased fracture length (81.5 ± 32.1 mm vs 56.9 ± 26.1 mm, p < 0.001) and decreased distance from fracture to proximal tibial pin site (84.5 ± 37.1 mm vs 126.9 ± 35.8 mm). Pins placed greater than 100 mm and 150 mm from the fracture eliminated 36/70 (51%) and 67/70 (96%) pin-plate overlaps, respectively. Pins placed with a PSF ratio greater than 1.5 and 2.0 eliminated 47/70 (67%), and 57/70 (81%) of pin-plate overlaps, respectively. Conclusions: Longer fractures, pins closer to the fracture, and decreased PSF ratio were associated with overlap. Placing proximal tibial pins more than 100 mm from the fracture eliminated most pin-plate overlaps. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Optimal glucose homeostasis requires exquisitely precise adaptation of the number of insulin-secreting β-cells in the islets of Langerhans. Insulin itself positively regulates β-cell proliferation in an autocrine manner through the insulin receptor (IR) signaling pathway. It is now coming to light that cannabinoid 1 receptor (CBIR) agonism/antagonism influences insulin action in insulin-sensitive tissues. However, the cells on which the CBIRs are expressed and their function in islets have not been firmly established. We undertook the current study to investigate if intraislet endogenous cannabinoids (ECs) regulate β-cell proliferation and if they influence insulin action. RESEARCH DESIGN AND METHODS--We measured EC production in isolated human and mouse islets and β-cell line in response to glucose and KC1. We evaluated human and mouse islets, several β-cell lines, and CB1R-null (CB1R-/-) mice for the presence of a fully functioning EC system. We investigated if ECs influence β-cell physiology through regulating insulin action and demonstrated the therapeutic potential of manipulation of the EC system in diabetic (db/db) mice. RESULTS--ECs are generated within β-cells, which also express CBIRs that are fully functioning when activated by ligands. Genetic and pharmacologic blockade of CBIR results in enhanced IR signaling through the insulin receptor substrate 2-AKT pathway in β-cells and leads to increased β-cell proliferation and mass. CBIR antagonism in db/db mice results in reduced blood glucose and increased β-cell proliferation and mass, coupled with enhanced IR signaling in β-cells. Furthermore, CBIR activation impedes insulin-stimulated IR autophosphorylation on β-cells in a Gαi-dependent manner. CONCLUSIONS--These findings provide direct evidence for a functional interaction between CB1R and IR signaling involved in the regulation of β-cell proliferation and will serve as a basis for developing new therapeutic interventions to enhance β-cell function and proliferation in diabetes. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) results from insulin resistance and β-cell dysfunction, in the setting of hyperglucagonemia. Glucagon is a 29 amino acid peptide hormone, which is secreted from pancreatic α cells: excessively high circulating levels of glucagon lead to excessive hepatic glucose output. We investigated if α-cell numbers increase in T2DM and what factor (s) regulate α-cell turnover. Leprdb/Leprdb (db/db) mice were used as a T2DM model and αTC1 cells were used to study potential α-cell trophic factors. Here, we demonstrate that in db/db mice α-cell number and plasma glucagon levels increased as diabetes progressed. Insulin treatment (EC50 = 2 nM) of α cells significantly increased α-cell proliferation in a concentration-dependent manner compared to non-insulin-treated α cells. Insulin up-regulated α-cell proliferation through the IR/IRS2/AKT/mTOR signaling pathway, and increased insulin-mediated proliferation was prevented by pretreatment with rapamycin, a specific mTOR inhibitor. GcgR antagonism resulted in reduced rates of cell proliferation in αTC1 cells. In addition, blockade of GcgRs in db/db mice improved glucose homeostasis, lessened α-cell proliferation, and increased intraislet insulin content in b cells in db/db mice. These studies illustrate that pancreatic α-cell proliferation increases as diabetes develops, resulting in elevated plasma glucagon levels, and both insulin and glucagon are trophic factors to α-cells. Our current findings suggest that new therapeutic strategies for the treatment of T2DM may include targeting α cells and glucagon. [ABSTRACT FROM AUTHOR]

Objective: Optimal glucose homeostasis requires exquisitely precise adaptation of the number of insulin-secreting \(\beta\)-cells in the islets of Langerhans. Insulin itself positively regulates \(\beta\)-cell proliferation in an autocrine manner through the insulin receptor (IR) signaling pathway. It is now coming to light that cannabinoid 1 receptor (CB1R) agonism/antagonism influences insulin action in insulin-sensitive tissues. However, the cells on which the CB1Rs are expressed and their function in islets have not been firmly established. We undertook the current study to investigate if intraislet endogenous cannabinoids (ECs) regulate \(\beta\)-cell proliferation and if they influence insulin action. Research Design and Methods: We measured EC production in isolated human and mouse islets and \(\beta\)-cell line in response to glucose and KCl. We evaluated human and mouse islets, several \(\beta\)-cell lines, and CB1R-null (CB1R\(^{−/−}\)) mice for the presence of a fully functioning EC system. We investigated if ECs influence \(\beta\)-cell physiology through regulating insulin action and demonstrated the therapeutic potential of manipulation of the EC system in diabetic (db/db) mice. Results: ECs are generated within \(\beta\)-cells, which also express CB1Rs that are fully functioning when activated by ligands. Genetic and pharmacologic blockade of CB1R results in enhanced IR signaling through the insulin receptor substrate 2-AKT pathway in \(\beta\)-cells and leads to increased \(\beta\)-cell proliferation and mass. CB1R antagonism in db/db mice results in reduced blood glucose and increased \(\beta\)-cell proliferation and mass, coupled with enhanced IR signaling in \(\beta\)-cells. Furthermore, CB1R activation impedes insulin-stimulated IR autophosphorylation on \(\beta\)-cells in a G\(\alpha_i\)-dependent manner. Conclusions: These findings provide direct evidence for a functional interaction between CB1R and IR signaling involved in the regulation of \(\beta\)-cell proliferation and will serve as a basis for developing new therapeutic interventions to enhance \(\beta\)-cell function and proliferation in diabetes.

The profound hypogonadism that occurs with androgen deprivation therapy (ADT) for prostate cancer (PCa) results in complications such as diabetes and metabolic syndrome that predispose to cardiovascular disease. Because phytoestrogens have been associated with an improvement in metabolic parameters, we evaluated their role in men undergoing ADT. Our objective was to evaluate the effects of high-dose isoflavones on metabolic and inflammatory parameters in men undergoing ADT. This was a randomized, double-blind, placebo-controlled, 12-week pilot study. Participants were randomly assigned to receive 20 g of soy protein containing 160 mg of total isoflavones vs taste-matched placebo (20 g whole milk protein). The study was conducted at a tertiary care center in the United States. Thirty-three men (isoflavones = 17, placebo = 16) undergoing ADT for PCa completed this pilot study. Mean age in the 2 groups was 69 years and the majority of men were Caucasians. Mean duration of ADT in both groups was approximately 2 years (P = .70). The 2 groups were well matched at baseline. After 12 weeks of intervention, there was no significant difference in either metabolic or inflammatory parameters between the 2 groups. We found that high-dose isoflavones over a course of 12 weeks do not improve metabolic or inflammatory parameters in androgen-deprived men.