Role of the Insulin-like Growth Factor System in Neurodegenerative Disease.

The insulin-like growth factor (IGF) system has paracrine and endocrine roles in the central nervous system. There is evidence that IGF signalling pathways have roles in the pathophysiology of neurodegenerative disease. This review focusses on Alzheimer's disease and Parkinson's disease, the two most common neurodegenerative disorders that are increasing in prevalence globally in relation to the aging population and the increasing prevalence of obesity and type 2 diabetes. Rodent models used in the study of the molecular pathways involved in neurodegeneration are described. However, currently, no animal model fully replicates these diseases. Mice with triple mutations in APP, PSEN and MAPT show promise as models for the testing of novel Alzheimer's therapies. While a causal relationship is not proven, the fact that age, obesity and T2D are risk factors in both strengthens the case for the involvement of the IGF system in these disorders. The IGF system is an attractive target for new approaches to management; however, there are gaps in our understanding that first need to be addressed. These include a focus beyond IGF-I on other members of the IGF system, including IGF-II, IGF-binding proteins and the type 2 IGF receptor.

Development of a Parallel Reaction Monitoring-MS Method To Quantify IGF Proteins in Dogs and a Case of Nonislet Cell Tumor Hypoglycemia.

Nonislet-cell tumor hypoglycemia (NICTH) is a rare paraneoplastic phenomenon well described in dogs and humans. Tumors associated with NICTH secrete incompletely processed forms of insulin-like growth factor-II (IGF-II), commonly named big IGF-II. These forms have increased bioavailability and interact with the insulin and IGF-I receptor causing hypoglycemia and growth-promoting effects. Immunoassays designed for human samples have been used to measure canine IGF-I and -II, but they possess some limitations. In addition, there are no validated methods for measurement of big IGF-II in dogs. In the present study, a targeted parallel reaction monitoring MS-based method previously developed for cats has been optimized and applied to simultaneously quantify the serum levels of IGF-I, IGF-II, and IGFBP-3, and for the first time, the levels of big IGF-II in dogs. This method allows the absolute quantification of IGF proteins using a mixture of QPrEST proteins previously designed for humans. The method possesses good linearity and repeatability and has been used to evaluate the IGF-system in a dog with NICTH syndrome. In this dog, the levels of big IGF-II decreased by 80% and the levels of IGF-I and IGFBP-3 increased approximately 20- and 4-times, respectively, after removal of the tumor.

Multi-sector perspectives on learning for interprofessional practice: lessons for higher education and organisational culture.

In order to build the evidence base for interprofessional education and practice, it is important to establish how the concepts and theories are understood by higher education providers, policy-makers, managers, and practitioners. Using an interdisciplinary research approach, and facilitated by the use of visual images, we undertook a discourse analysis of interviews and discussions around definitions, competencies, and cultures of learning for interprofessional practice in the context of child health and social care in Scotland. Challenges to interprofessional practice were seen as generated within professional hierarchies and the complicatedness of working with chronic or multisystem disease. In order to work collaboratively, individual practitioners should understand the boundaries of their own knowledge and skills and demonstrate the capacity for interpersonal communication (within and between professions), as well as problem-solving and dealing with uncertainty. While there was agreement on these as key learning needs for collaborative working, the term interprofessional education was rarely used in practice by the interviewees and there was perception of a gap between university and workplace settings in supporting learning for interprofessional practice. It is recommended that educational frameworks acknowledge that the interprofessional learning journey is influenced by context and organisational culture.

Preregistration nursing students' perspectives on the learning, teaching and application of bioscience knowledge within practice.

AIMS AND OBJECTIVES: This paper aims to explore student nurses' experiences of bioscience learning, teaching and application within the practice setting. It draws upon the social learning theory of communities of practice to consider the issues raised. BACKGROUND: The teaching of bioscience within many nursing curricula has shifted from traditional to more integrated approaches. Student nurses recognise bioscience as a valuable component of their studies, but many find it challenging. The focus of previous research in this area has often focussed on bioscience learning in theoretical rather than practice settings. DESIGN: A phenomenological study. METHODS: Data were collected via focus group or interview with a total of seven students across two campuses in a Scottish university. Participants were offered the opportunity to share their experiences at both the end of year one and year two of their studies. A thematic analysis was undertaken independently then jointly by the authors. RESULTS: The findings suggest that although participants recognise the value of bioscience within practice settings, they found that opportunities for learning were often limited. Bioscience-related learning, teaching and application was perceived to have been given less legitimacy by the practice setting than other aspects of placement activity. To enhance bioscience approaches participants expressed a desire for more structured and integrated approaches within both practice and university along with further peer learning opportunities. CONCLUSIONS: Students recognise that bioscience knowledge is important in relation to the provision of safe and effective care. They request greater structure and consistency in relation to the learning, teaching and application of this topic during their placements. RELEVANCE TO CLINICAL PRACTICE: Those with a stake in educating nurses within clinical settings may find the views of student nurses on the topic of bioscience learning useful when planning and facilitating placement experiences.

Higher serum concentrations of tyrosine and glutamate in schizophrenia patients treated with clozapine, compared to in those treated with conventional antipsychotics.

RATIONALE: The effect of long-term treatment with the atypical antipsychotic clozapine on the serum amino acid profile in schizophrenia patients has not previously been studied. OBJECTIVES: The aim of this study was to compare serum amino acid patterns in patients on long-term clozapine treatment with long-term conventional antipsychotic treatment, and their relationships to insulin resistance and antipsychotic serum concentrations. METHODS: Thirty-three patients with schizophrenia or schizoaffective disorder on long-term treatment (mean 8.3 years) with clozapine (n=20) or conventional antipsychotics (n=13) were studied. Amino acids were quantified in fasting serum samples by ion exchange chromatography and markers of insulin resistance and antipsychotic drug concentrations were determined by standard methods. RESULTS: Several amino acids, most notably tyrosine and glutamic acid, were elevated above the reference range in several patients receiving clozapine. Additionally, significantly higher mean values of tyrosine (1.5-fold, p=0.001), glutamic acid (2-fold, p=0.0005) and six other amino acids were observed in the clozapine group than in the conventional antipsychotic group. Several amino acids were related to insulin resistance in both treatment groups. CONCLUSIONS: In this study, we show that serum tyrosine and glutamic acid concentrations are markedly elevated in patients on long-term clozapine treatment, compared to patients on long-term conventional antipsychotic treatment. These findings are of importance since these two amino acids have been implicated in the pathophysiology of schizophrenia.

Effect of the 'Pilates stance' and Pilates-based matwork training on measurements of height, waist circumference, and interscapular distance.

BACKGROUND: Standardised guidelines for stance are used to improve interobserver reliability in anthropometric measurements in clinical practice. A key feature of the stance in Pilates is the 'drawing in and up' of the abdomen. The aim of this study was to study the impact of the Pilates stance on height, waist circumference and interscapular distance, compared to that recommended in clinical practice. METHODS: 48 healthy females (median age 60 years) were assessed before and after 10-week Pilates-based matwork training. One Pilates expert and one novice took independent measurements of weight, height, waist circumference and interscapular distance (ISD). RESULTS: Pilates stance, compared to Normal, increased height by up to 2.7 cm and decreased waist up to 5.2 cm (each P < 0.001, repeated measures ANOVA). ISD decreased up to 14 mm (P < 0.001) and this decrease was greater after training (P < 0.001). After controlling for age and length of time learning Pilates, greater baseline ISD predicted a greater change in ISD after the intervention. Effect of Pilates stance was greater when the expert took the measurements (each P ≤ 0.001). CONCLUSIONS: Activation of trunk muscles in the Pilates stance increases height and decreases waist circumference, compared to the stance recommended in UK healthcare settings. A decrease in ISD was observed, which was greater after a Pilates-based matwork programme. There are significant inter-observer differences, therefore current clinical guidelines for stance are recommended for repeated anthropometry. The value of the Pilates stance in improving posture and the role of ISD as a marker, should be further studied in various contexts, including clinical settings.

Pubertal stage and measures of adiposity in British schoolchildren.

BACKGROUND: Puberty is a critical period in the development of obesity. Body mass index (BMI), waist circumference and skin-fold thickness are used generally as estimates of body fat in children and adults. AIM: To identify a marker of adiposity that is independent of pubertal status and determine its relationship to physical fitness in adolescence. SUBJECTS AND METHODS: Girls (n = 147) and boys (n = 100) from year 8 in three Welsh schools self-reported Tanner stages. Anthropometric measurements of adiposity were made and aerobic fitness estimated with a 20-metre shuttle-run test. RESULTS: Children in early and late puberty were of similar chronological age. BMI strongly correlated with height in early puberty in girls (r = 0.366, p < 0.001) and boys (r = 0.594, p < 0.001), but not in late puberty. Waist-to-height ratio adjusted for the effect of height on waist measurements; and correlated with percentage fat mass in early and late puberty in girls (r = 0.865 and r = 0.772, both p < 0.001) and boys (r = 0.868 and r = 0.877, both p < 0.001). Physical fitness score was inversely related to waist-to-height ratio, with similar regression lines in early and late puberty, in girls (r = - 0.545, p < 0.001 and r = - 0.362, p = 0.005) and boys (r = - 0.490, p < 0.001 and r = - 0.400, p = 0.003). CONCLUSION: Pubertal status should be taken into account in adjusting weight for height in adolescents. Waist-to-height ratio is a convenient and appropriate measure of adiposity during puberty.

Case-based training of evidence-based clinical practice in primary care and decreased mortality in patients with coronary heart disease.

PURPOSE: We investigated the 10-year mortality rates in a trial that tested a case-based intervention in primary care aimed at reducing the gap between evidence-based goals and clinical practice in patients with coronary heart disease (CHD). METHODS: A prospective randomized controlled pragmatic trial was undertaken in a primary care setting. New evidence-based guidelines, with intensified lipid-lowering recommendations in CHD, were mailed to all general practitioners in the region and presented at a lecture in 1995. General practitioners (n = 54) and patients with CHD (n = 88) were assigned according to their primary health care center to 2 balanced groups and randomly allocated to usual care as a control or to an active intervention. General practitioners in the intervention group participated in repeated case-based training during a 2-year period. Patients whose CHD was treated by specialists (n = 167) served as an internal specialist comparison group. Altogether, 255 consecutive patients were included. Cox regression analysis was used to detect any survival benefit of the intervention. RESULTS: At 10 years, 22% of the patients in the intervention group had died as compared with 44% in the control group (P = .02), with a hazard ratio of 0.45 (95% confidence interval, 0.20-0.95). This difference was mainly due to reduced cardiovascular mortality in the intervention group (P = .01). In addition, the mortality rate of 22% in the intervention group was comparable to the rate of 23% seen in patients treated by a specialist. CONCLUSIONS: Use of case-based training to implement evidence-based practice in primary care was associated with decreased mortality at 10 years in patients with CHD.

Stereotyping at the undergraduate level revealed during interprofessional learning between future doctors and biomedical scientists.

Interprofessional education (IPE) involving undergraduate health professionals is expected to promote collaboration in their later careers. The role of IPE between doctors and biomedical scientists has not been explored at the undergraduate level. Our aim was to introduce IPE sessions for medical and biomedical students in order to identify the benefits and barriers to these groups learning together. Medical and biomedical students together discussed laboratory results, relevant literature, and ideas for developing new diagnostic tools. The programme was evaluated with questionnaires and interviews. While there was general support for the idea of IPE, medical and biomedical students responded differently. Biomedical students were more critical, wanted more explicit learning objectives and felt that their professional role was often misunderstood. The medical students were more enthusiastic but regarded the way the biomedical students communicated concerns about their perceived role as a barrier to effective interprofessional learning. We conclude that stereotyping, which can impede effective collaborations between doctors and biomedical scientists, is already present at the undergraduate level and may be a barrier to IPE. Effective learning opportunities should be supported at the curriculum level and be designed to specifically enable a broad appreciation of each other's future professional roles.

Relationship between abdominal adiposity, cardiovascular fitness, and biomarkers of cardiovascular risk in British adolescents.

BACKGROUND: Puberty is a critical time in the development of overweight and obesity. The aim of this study was to examine relationships between measures of adiposity, cardiovascular fitness, and biomarkers of cardiovascular disease risk in adolescents. METHODS: In a cross-sectional study design, 129 girls and 95 boys aged 12.9-14.4 years at various stages of puberty were included, along with their mothers (n = 217) and fathers (n = 207). Anthropometric assessments of adiposity were made, along with cardiovascular physical fitness, using the 20-m shuttle run test, and biomarkers associated with cardiovascular risk, including glucose, insulin, triglyceride, fibrinogen, and C-reactive protein (CRP) concentrations. RESULTS: Waist-to-height ratio values were similar in boys and girls and correlated positively with diastolic blood pressure, insulin, triglyceride, fibrinogen, and CRP concentrations, and inversely with cardiovascular fitness scores. Skinfold thickness measurements were higher in girls. High-molecular-weight adiponectin concentrations were lower in boys than girls, particularly in late puberty, and CRP levels were higher. Cardiovascular fitness, maternal body mass index (BMI), and paternal BMI contributed independently to the variance in waist measurements in girls and boys. Gender, triceps skinfold thickness, and weight-to-height ratio, but not parental BMI, contributed independently to the variance in cardiovascular fitness. CONCLUSION: There is a relationship between measures of adolescent adiposity and parental weight that involves factors other than cardiovascular fitness. Adolescent boys have relatively more abdominal fat than girls and a tendency to have a proinflammatory profile of biomarkers. These observations suggest that family and social environmental interventions are best undertaken earlier in childhood, particularly among boys.

The Role of Insulin-Like Growth Factors and Insulin-Like Growth Factor-Binding Proteins in the Nervous System.

The insulin-like growth factors (IGF-I and IGF-II) and their receptors are widely expressed in nervous tissue from early embryonic life. They also cross the blood brain barriers by active transport, and their regulation as endocrine factors therefore differs from other tissues. In brain, IGFs have paracrine and autocrine actions that are modulated by IGF-binding proteins and interact with other growth factor signalling pathways. The IGF system has roles in nervous system development and maintenance. There is substantial evidence for a specific role for this system in some neurodegenerative diseases, and neuroprotective actions make this system an attractive target for new therapeutic approaches. In developing new therapies, interaction with IGF-binding proteins and other growth factor signalling pathways should be considered. This evidence is reviewed, gaps in knowledge are highlighted, and recommendations are made for future research.

Development of a Pilates Teaching Framework from an international survey of teacher practice.

OBJECTIVE: Pilates is used increasingly in a variety of clinical settings. However, there is lack of clarity in the literature as to what is meant by the term. Teachers incorporating apparatus based on the designs of Joseph Pilates (1883-1967) into their practice refer to themselves as Comprehensive Teachers, and this group divides itself further into Classical and Contemporary practice. The aim of this research was to explore the meanings of these terms with Comprehensive Teachers and to develop a framework that reflects current views and practice. METHOD: Online international survey of Pilates Teachers through closed Facebook forums. Open questions were used to elicit views of the definition and practice of Pilates, and how standards should be set across the sector. RESULTS: Of 109 participants, 35% were based in the UK and 32% in the USA; 48% identified as Classical teachers, 32% as Contemporary, 5% as both and 15% as Matwork instructors. A thematic analysis of the qualitative data revealed agreement on the scope and content of Classical and Contemporary Comprehensive Pilates, however the discourse indicated there might be stereotyping about each other's practice. Classical teachers, for example, spoke of their own practice as authentic while Contemporary teachers used terms such as strict and inflexible for Classical practice. However, members of either group may incorporate both Classical and Contemporary approaches within their practice. We have designed a Pilates Teaching Framework to take into account the types of apparatus, the types of exercises and the order in which the exercises are executed. CONCLUSIONS: A framework that emphasises Pilates teaching rather than teacher practice is proposed for consistency and clarity when describing Pilates in professional and public contexts.

Insulin-like growth factor binding protein 1 as a novel specific marker of hepatic insulin sensitivity.

BACKGROUND AND AIMS: The liver is the main source and insulin the main regulator of IGF binding protein 1 (IGFBP-1) in humans. Here we examined how serum IGFBP-1 concentrations are related to directly measured hepatic insulin sensitivity and liver fat content in humans. METHODS: We measured fasting serum (fS) IGFBP-1 concentrations and liver fat content by proton magnetic resonance spectroscopy in 113 nondiabetic subjects. In addition, hepatic insulin sensitivity was measured using the euglycemic hyperinsulinemic clamp (insulin 0.3 mU/kg.min) technique in combination with the infusion of [3-(3)H]glucose in 78 subjects. RESULTS: fS-IGFBP-1 concentrations were inversely related to liver fat content (r = -0.38, P < 0.0001). Of circulating parameters, fS-IGFBP-1 was better correlated to hepatic insulin sensitivity (r = 0.48, P < 0.0001) than fS-insulin (r = -0.42, P = 0.0001), fS-C-peptide (r = -0.41, P = 0.0002), fS-triglyceride (r = -0.33, P = 0.003), or fS-high-density lipoprotein cholesterol (r = 0.30, P = 0.007). In multiple linear regression analyses, body mass index (P < 0.0001) and fS-IGFBP-1 (P = 0.008), but neither age nor gender, were independently associated with hepatic insulin sensitivity (P < 0.0001 for ANOVA). Neither fS-insulin nor fS-C-peptide were independent determinants of hepatic insulin sensitivity after adjusting for age, gender, and body mass index. CONCLUSIONS: fS-IGFBP-1 is inversely correlated with liver fat and is an obesity-independent and liver-specific circulating marker of hepatic insulin sensitivity.

Diabetic osteopathy and the IGF system in the Goto-Kakizaki rat.

OBJECTIVE: Diabetes mellitus is associated with an increased risk of osteopenia, fracture and Charcot arthropathy. Abnormalities of the IGF system commonly observed in diabetes may underlie this "diabetic osteopathy" as IGF-I and its binding proteins (IGFBPs) have been shown to affect osteoblast and osteoclast activity. DESIGN: In type-2 diabetic and control rats we analyzed IGF-I and IGFBP-1 and -4 levels in serum, and notably, also the IGF-I levels in cortical bone, ankles and vertebrae by immunoassays. Osteopathy was assessed by radiography and dual energy X-ray absorptiometry. RESULTS: In the diabetic rats IGF-I was significantly reduced in serum and diaphyseal bone while IGFBP-1 and IGFBP-4 were increased in serum. The periosteal and endosteal diameters were increased in the diaphysis of humerus and tibia (changes similar to those in elderly humans) while bone mineral density was reduced in long bone metaphyses and vertebrae. CONCLUSIONS: Our study demonstrates both systemic and local disturbances of the IGF-system in rats with type-2 diabetes, consistent with the observed enhanced endosteal erosion in long bone diaphyses, and osteopenia in metaphyses and vertebrae. Whether similar IGF-system changes contribute to osteopathy in patients with diabetes and if treatment of diabetes can reverse the osteopathy has yet to be explored.

Effect of insulin treatment on circulating insulin-like growth factor I and IGF-binding proteins in cats with diabetes mellitus.

BACKGROUND: Insulin-like growth factor-I (IGF-I) is used to screen for acromegaly in diabetic cats. In humans, most circulating IGF-I forms ternary complexes (TC) with IGF-binding protein (IGFBP-3) and an acid-labile subunit. Compared to humans, the amount of TC in cats is more variable. Insulin-like growth factor-I concentrations are reported to increase during insulin treatment, more rapidly in cats achieving remission. OBJECTIVES: To investigate (i) factors associated with circulating IGF-I concentrations, including IGFBP-profiles (ii) effect of insulin treatment on IGF-I concentrations and (iii) IGF-I as prognostic marker of diabetes mellitus remission. ANIMALS: Thirty-one privately owned diabetic cats of which 24 were followed 1 year, and 13 healthy cats. METHODS: Prospective study. Serum insulin, IGF-I, glucose, and fructosamine concentrations were measured. IGF-binding forms were determined by chromatography in 14 diabetic and 13 healthy cats; and IGF-I, IGF-II, IGFBP-3, and IGFBP-5 by mass spectrometry in 3 cats achieving remission. RESULTS: Insulin-like growth factor-I median (interquartile range) before start of insulin treatment was 300 (160-556) ng/mL. Insulin-like growth factor-I was positively associated with TC (P < .0001) and endogenous insulin (P = .005) and negatively associated with fructosamine (P < .0001). Median IGF-I was higher 2-4 weeks after start of insulin treatment compared with baseline (300 versus 670 ng/mL, P = .0001) and predicted future remission (P = .046). In cats that went into remission, the amount of TC and IGFBP-3 increased, suggesting increase in IGF-I is dependent on TC formation. CONCLUSIONS: Insulin treatment should be accounted for when interpreting IGF-I in diabetic cats. Insulin-like growth factor-I 2-4 weeks after initiation of insulin treatment shows promise as prognostic marker for remission in diabetic cats.

The Role of the Growth Hormone/Insulin-Like Growth Factor System in Visceral Adiposity.

There is substantial evidence that the growth hormone (GH)/insulin-like growth factor (IGF) system is involved in the pathophysiology of obesity. Both GH and IGF-I have direct effects on adipocyte proliferation and differentiation, and this system is involved in the cross-talk between adipose tissue, liver, and pituitary. Transgenic animal models have been of importance in identifying mechanisms underlying these interactions. It emerges that this system has key roles in visceral adiposity, and there is a rationale for targeting this system in the treatment of visceral obesity associated with GH deficiency, metabolic syndrome, and lipodystrophies. This evidence is reviewed, gaps in knowledge are highlighted, and recommendations are made for future research.

An individual approach to feline diabetes care: a case report and literature review.

BACKGROUND: Achieving insulin independence is emerging as a realistic therapeutic goal in the management of feline diabetes mellitus. CASE PRESENTATION: The management of an 11-year-old spayed female Burmese cat presenting with diabetes mellitus after corticosteroid administration is described. Remission was achieved after the frequency of insulin administration was increased to four times a day, and supported by intensive home blood glucose monitoring and a high protein, low carbohydrate diet. CONCLUSION: Owners are important collaborators in feline diabetes care and, with intensive home monitoring, more frequent insulin treatment may lead to remission without hypoglycemia. More frequent insulin injections than recommended in the literature may be necessary to achieve glycemic control and used as an alternative to a longer-acting insulin.

Altered response of insulin-like growth factor-binding protein 1 to nutritional deprivation in type 2 diabetes mellitus.

Circulating insulin-like growth factor-binding protein 1 (IGFBP-1) normally has a close inverse relationship to insulin secretion, which results in a characteristic diurnal variation. However, in type 2 diabetes the correlation with insulin may be lost and IGFBP-1 concentrations relatively increased. The aim of this study was to determine the effect of nutritional deprivation on the diurnal patterns of IGFBP-1 regulation in type 2 diabetes mellitus. After a baseline assessment period, food intake was reduced over 48 hours to 627.6 kJ/d (150 kcal/d) for 72 hours and increased again over 24 hours to baseline (refeeding). Blood samples were taken at 2-hour intervals, for 24 hours in the baseline period, 48 hours during nutritional deprivation, and 24 hours during refeeding. Six individuals with type 2 diabetes were compared with 2 groups that were selected for normal fasting glucose and insulin levels and comprised 6 obese and 6 lean subjects. During energy (caloric) restriction, fasting insulin levels decreased to a similar extent in each study group. At baseline, IGFBP-1 concentrations were similar in each of the study groups and at the end of the period of energy (caloric) restriction the 6:00 AM fasting levels had increased by 144% in the obese control group and by 245% in the lean individuals (each P < .001). In the patients with type 2 diabetes there was a blunted increase in IGFBP-1 concentrations with nutritional deprivation by 33% compared with baseline. During refeeding after nutritional deprivation the IGFBP-1 response to insulin was restored in the individuals with diabetes. In conclusion, patients with type 2 diabetes mellitus have altered IGFBP-1 regulation, relating to impaired hepatic insulin sensitivity, which improves after a period of energy (caloric) restriction.

Insulin-like growth factor I in cats: validation of an enzyme-linked immunosorbent assay and determination of biologic variation.

BACKGROUND: Insulin-like growth factor I (IGF-I) measurements are used in veterinary medicine for diagnosing growth hormone disorders. IGF-I assays are subject to interference by IGF-binding proteins (IGFBP) which may not be efficiently removed by standard extraction methods. Adding excess IGF-II during analysis may improve accuracy. OBJECTIVES: The purpose of the study was to validate a commercial human IGF-I ELISA which uses excess IGF-II for feline samples and to evaluate biologic variation. METHODS: Precision was determined by calculating the coefficient of variation (CV). Accuracy was determined by recovery after removal of IGFBP, addition of IGF-I, and linear dilution after the addition of IGFBP. Biologic variation was determined by repeated sampling in 7 cats. RESULTS: There was interference by IGFBP in the high measuring range, resulting in falsely low IGF-I concentrations. This was overcome by the addition of high concentrations of IGF-II. Untreated serum had a measured/expected ratio of 98-115% compared to serum where IGFBP had been removed. Recovery after the addition of IGF-I was 83-112%. Inter- and intra-assay CVs ranged from 2.4% to 5.0% which is within the minimum acceptance criteria based on biologic variation. The reference interval of IGF-I was wide (90-1207 ng/mL) and there was a significant association between body weight and ln IGF-I (P < .000001). CONCLUSIONS: This human ELISA is suitable for feline samples, but interfering IGFBP can cause falsely low concentrations. It is recommended to dilute samples such that IGF-I is < 28 ng/mL on the standard curve to grant for sufficient IGF-II for binding of interferent IGFBP.

Gender-specific pattern of insulin-like growth factor-binding protein-3 protease activity in mouse thyroid.

There is evidence that the IGF system plays an important role in the growth and function of the thyroid gland. Proteolysis is an important posttranslational process that modulates the affinity of IGF binding proteins (IGFBPs) to IGFs, thus regulating their activity. IGFBP-3 has been shown to be cleaved by members of the kallikrein family, some of which are expressed in human thyroid and are characterized by regulation by steroid hormones. The aim of this study was to determine whether IGFBP-3 protease activity is present in mouse thyroid tissue and to characterize its activity by gender and nutrition. Male and female BALB/c mice, aged 16 wk, were studied in the fasted state, or after 1-h or 4-h refeeding. IGFBP protease activity was present in thyroid tissue and resulted in a decrease in IGFBP-3 affinity for IGF-I. The activity was inhibited by 10 mM ZnCl(2), activated by CaCl(2), and was substantially greater in tissue from male mice compared with that from female animals. These properties and the pattern of effect of a panel of protease inhibitors were consistent with this protease being a member of the tissue kallikrein family. Serum inhibited the proteolytic effect of thyroid extracts. There was no effect of nutrition. In conclusion, the degree of activity of IGFBP-3 protease in mouse thyroid tissue is gender specific and is likely to lead to an increased IGF availability in male mice.