Catherine Loveland-Jones

Insulin Regulates the Unfolded Protein Response in Human Adipose Tissue

Endoplasmic reticulum (ER) stress is increased in obesity and is postulated to be a major contributor to many obesity-related pathologies. Little is known about what causes ER stress in obese people. Here, we show that insulin upregulated the unfolded protein response (UPR), an adaptive reaction to ER stress, in vitro in 3T3-L1 adipocytes and in vivo, in subcutaneous (sc) adipose tissue of nondiabetic subjects, where it increased the UPR dose dependently over the entire physiologic insulin range (from ∼35 to ∼1,450 pmol/L). The insulin-induced UPR was not due to increased glucose uptake/metabolism and oxidative stress. It was associated, however, with increased protein synthesis, with accumulation of ubiquitination associated proteins, and with multiple posttranslational protein modifications (acetylations, methylations, nitrosylations, succinylation, and ubiquitinations), some of which are potential causes for ER stress. These results reveal a new physiologic role of insulin and provide a putative mechanism for the development of ER stress in obesity. They may also have clinical and therapeutic implications, e.g., in diabetic patients treated with high doses of insulin.

Comparison of In Vivo Effects of Insulin on SREBP-1c Activation and INSIG-1/2 in Rat Liver and Human and Rat Adipose Tissue

The stimulatory effects of insulin on de novo lipogenesis (DNL) in the liver, where it is an important contributor to non‐alcoholic fatty liver disease (NAFLD), hepatic and systemic insulin resistance, is strong and well established. In contrast, insulin plays only a minor role in DNL in adipose tissue. The reason why insulin stimulates DNL more in liver than in fat is not known but may be due to differential regulation of the transcription and post‐translational activation of sterol regulatory element binding proteins (SREBPs). To test this hypothesis, we have examined effects of insulin on activation of SREBP‐1c in liver of rats and in adipose tissue of rats and human subjects.

Squamous cell carcinoma of the nipple following radiation therapy for ductal carcinoma in situ: a case report

IntroductionRadiation-induced nonmelanoma skin cancer was first reported seven years after the discovery of X-rays, but has received relatively little consideration in the literature. Specifically, nonmelanoma skin cancer after conservative surgery and radiation for early stage breast cancer has not been well studied. We report the case of a woman who developed squamous cell carcinoma of the nipple nine years after conservative surgery and radiation for ductal carcinoma in situ of the ipsilateral breast. We also review the relevant literature available to date.Case presentationA 66-year-old African-American woman presented to the hospital with a non-healing ulcer of the right nipple. Her past medical history was significant for right breast ductal carcinoma in situ for which she had undergone lumpectomy and whole breast radiation therapy nine years previously. Mammography and magnetic resonance imaging studies were negative for recurrent breast cancer. However, the latter demonstrated abnormal enhancement in the nipple-areolar region. An incisional biopsy of the lesion demonstrated invasive squamous cell carcinoma. Subsequently, the patient underwent wide excision of the nipple-areolar complex. Sentinel lymph-node biopsy was offered but our patient declined. She was considered to have local disease and hence no further treatment was recommended.ConclusionThis case represents the first reported occurrence of squamous cell carcinoma of the nipple to follow conservative surgery and radiation for ductal carcinoma in situ of the ipsilateral breast. It is likely that radiation overexposure resulted in a radiation burn and subsequent radiodermatitis, placing it at risk for squamous cell carcinoma. A diagnosis of squamous cell carcinoma should be considered in a patient with a nipple lesion following radiation therapy for breast cancer.

A new model of arteriovenous fistula to study hemodialysis access complications.

Purpose This report presents a new animal model of arteriovenous fistula (AVF) with attention given to surgical techniques as well as hemodynamic and pathologic measurements. Of note, this model was created with a tunneled central catheter with the purpose of studying therapeutic interventions, including hemodialysis. Methods Side-common carotid artery to end-external jugular vein AVFs were created in eight minipigs. A tunneled central catheter was also placed in the internal jugular vein. After 28 days, hemodynamic measurements of AVF flow and stenosis were performed. The minipigs were then euthanized and the AVFs were harvested for pathologic measurements of neointimal hyperplasia and thrombus volumes. In order to account for variable size of the AVFs, percentage luminal stenosis and degree of intima–media thickening were calculated. Results After 28 days, all eight AVFs remained patent. On average, 19% of arterial blood flow that approached the AVF traveled through the anastomosis. The average luminal stenosis by angiogram was 61.1%. The average neointimal hyperplasia and thrombus volumes were 1.4×108 and 3.8×108 μm3, respectively. The average luminal stenosis and intima–media thickening were 65.2% and 430.4 μm, respectively. Conclusions This AVF model is ideal because of the relative ease of surgery and husbandry, lack of complications, as well as consistent and rapid development of the neointimal lesion which underlies AVF failure.

How to Develop Faculty Mentors

The absence of financial incentives is a major obstacle to developing faculty mentors. Structured approaches are needed to develop faculty mentors. Recruiting individuals with vested interests, providing protected time, and monetary and career incentives will help develop faculty mentors. Structured written evaluation and objective verbal feedback are mandatory for optimal development of faculty mentors. There are resolvable and irresolvable causes of faculty discontent. Current needs to develop faculty mentors provide opportunities for research.

Response to Comment on Boden et al. Insulin Regulates the Unfolded Protein Response in Human Adipose Tissue. Diabetes 2014;63:912–922

We thank Drs. Lieske and Birkenfeld (1) for their comments. We agree that in our article (2) we did not address the question of whether or not the activating effects of insulin on endoplasmic reticulum …

Mentoring International Medical Graduates

The number of IMGs in US surgery continues to increase. IMG applicants should be evaluated as to their overall qualifications rather than solely as an IMG. IMG mentoring must be implemented early, preferably by designated IMG faculty and resident mentors. To optimally mentor IMGs it is necessary to understand their unique challenges upon entering a new country and medical culture. Structured mentoring programs efficaciously mentor IMGs entering US residencies.

Why Surgical Mentoring is Important and Evidence That it Makes a Difference

Most successful surgeons have had accomplished surgical mentors. Mentoring provides evidence-based personal and career benefits to the mentee. Immense personal satisfaction and a prolonged opportunity to help others are the principal benefits to the surgical mentor.

Mentoring Women Surgeons

More women are becoming surgeons. Women bring distinct strengths to surgery. Issues specific to women surgeons must be understood to provide effective mentoring. Male mentors and colleagues must know what is offensive to women surgeons. The American College of Surgeons and the Association of Women Surgeons have established programs to mentor women. Mentors should encourage women surgeons to seek teaching and leadership positions, integrate lifestyle issues, obtain multiple mentors and establish networking contacts.

How to Choose a Mentor

Mentors should be selected early in the mentee’s career. Mentees require multiple mentors throughout their careers. The selection process should be initiated by the mentee. The mentee must be well prepared for meetings with the prospective mentor and make appropriate follow-up. The mentee must be proactive to maintain mentoring relationships. Most mentoring relationships are transient.