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Dr Tarsem Sahota

Job: Post Doctoral Fellow

Faculty: Health and Life Sciences

School/department: Leicester School of Pharmacy

Address: De Montfort University, The Gateway, Leicester, LE1 9BH.

T: +44 (0)116 250 6972 / +44(0)116 250 6220

E: ssahota@dmu.ac.uk

W: https://www.dmu.ac.uk/hls

 

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Personal profile

  • Development of artificial pancreas
  • Delivery of insulin by self regulation
  • Structure and behaviour of insulin in solution
  • Polymerisation and covalent structures of proteins and polysaccharides, e.g. lectins and glucose polymers
  • In vivo studies
  • Development of a triggered dermatological formulation for the treatment of psoriasis
  • Physiological parameters for exercise in diabetes.

Research group affiliations

  • Department of Diabetes and Endocrinology, University Hospitals of Leicester NHS Trust
  • National Physical Laboratory
  • IOCT, De Montfort University
  • Renfrew Group, Leicester

Publications and outputs

  • Glucose lowering strategies with insulin
    dc.title: Glucose lowering strategies with insulin dc.contributor.author: Taylor, M. Joan; Sahota, T. S.; Chauhan, Krishan P dc.description.abstract: People with type 1 diabetes must use insulin and a large fraction of those with type 2 condition also do so. Many therefore struggle with the unpredictable balancing of insulin dose with calorie intake and utility. A healthy pancreas makes meticulous adjustment on a continuous basis that present therapeutic insulin administration cannot match. However, much progress has been made to make it simpler to inject both background and fast-acting boost insulins with a view to better mimicking normal pancreatic output. The present fast insulins are reviewed with accent on the primary amino acid structures of the biosynthetic types that diffuse more quickly than regular insulin that associates in hexamers. This makes boost doses kinetically and clinically more effective, allowing people to inject better estimated boost and corrective doses. Formulation advances are discussed for their present and potential contributions. The newer slow-acting insulins are also described and compared, their advantage also being kinetic with a lower likelihood of inducing overnight hypoglycaemia when used optimally. Finally, the appreciation of the advantages of alternative routes of administration such as oral and peritoneal are included in this review because of the possibility of altering the hepatic to peripheral ratio, the reasons for which are more effective but less obesogenic insulin activity. The logistics of oral insulin are summarised in terms of the risks to the insulin structure, the facilitation of paracellular uptake at the apical surface and the paradoxically advantageous hepatic first pass. Other non-invasive routes are also included in the review. dc.description: open access journal
  • Gels for constant and smart delivery of insulin
    dc.title: Gels for constant and smart delivery of insulin dc.contributor.author: Taylor, M. Joan; Chauhan, Krishan P; Sahota, T. S. dc.description.abstract: The focus of this review is the role of gelatinous materials for oral, transdermal and peritoneal insulin platforms as alternatives to the ubiquitous subcutaneous depot approach. Hydrogels that form hydrated, cohesive materials and the topologically complex micellar types can add ligand interaction, bond vulnerability and rheological characteristics to develop reliable programmed release, including closed loop (automated basal and bolus) activity in non-oral routes. In addition, the potential protection of the protein and likely increased paracellular uptake mean that orally active insulin is feasible. While unlikely to be suitable for closed loop delivery, the driver for gut absorption is not only to increase the convenience and decrease dosage trauma, but to target the mesentery-portal vasculature rather than peripheral tissue, thus improving hepatic glycogen equilibrium and reducing the obesogenic effect and hypoglycaemic episodes.
  • Insulin Solution Stability and Biocompatibility with Materials Used for an Implantable Insulin Delivery Device Using Reverse Phase HPLC Methods
    dc.title: Insulin Solution Stability and Biocompatibility with Materials Used for an Implantable Insulin Delivery Device Using Reverse Phase HPLC Methods dc.contributor.author: Jacob, Dolly; Tomlins, Paul; Taylor, M. Joan; Sahota, T. S. dc.description.abstract: Abstract: Insulin (Humulin® R IU500) has been delivered from an implantable artificial pancreas in diabetic rats and pigs. The artificial pancreas which was implanted in the peritoneum was fabricated from several biocompatible materials such as polycarbonate, stainless steel, polyurethane, titanium and a polyurethane resin. The device also contains a glucose responsive smart gel which controls the di usion of insulin dependent on the surrounding glucose environment. As the insulin reservoir is refillable and in contact with the device materials, assessing its biocompatibility with these various device component materials was conducted. Insulin can undergo chemical degradation mainly via a deamidation reaction on glutamine and asparagine residues rendering its biological hormone functionality. Two Reverse Phase High Performance Liquid Chromatography (RP-HPLC) methods were developed and validated for detection of insulin and degradant Asn A21 desamido insulin (method A) and insulin and degradant Asn B3 desamido insulin (method B). Material biocompatibility studies show that stainless steel and titanium are suitable for an implantable insulin delivery device design over a 31-day period. The use of polycarbonate and polyurethane could be considered if the insulin reservoir in the device was only to remain in the device for less than 11 days after which time there is a loss in cresol which acts in a protective capacity for insulin stability. dc.description: open access article
  • The effects of a combined aerobic and resistance exercise programme on insulin resistance among prediabetes subjects
    dc.title: The effects of a combined aerobic and resistance exercise programme on insulin resistance among prediabetes subjects dc.contributor.author: Alharbi, Bander; Alsubaie, Nawal; Sahota, T. S.; Taylor, M. Joan dc.description.abstract: Aim: Insulin resistance is a common health disorder that contributes to developed overt diabetes among prediabetes subjects. The aim of the study is to examine the effects of a combined programme of aerobic and resistance exercise on insulin resistance among prediabetes subjects (Pre-D) using Oral Glucose Tolerance Test (OGTT) as a tool to define the improvement in insulin resistance. Method: 20 prediabetes subjects were asked to join a supervised combined exercise program consists of 30 min of resistance exercise followed by 20 min cycling twice at moderate-intensity a week for 6 weeks. Result: a significant improvement in Blood Glucose (BG) after combination exercise at two occasions when compared to BG before exercise (Pre S1), after 1st exercise session (Post S1) and at the end of intervention trial (Post S12). Conclusion: The result of this study has shown that 6 weeks of moderate-intensity exercise combined with aerobic and resistance exercise program had significantly ameliorated insulin resistance among Pre-D. dc.description: open access article
  • The effects of (a combined exercise programme aerobic and resistance) on blood glucose and incretin hormone that could control the diabetes in type 2 diabetes.
    dc.title: The effects of (a combined exercise programme aerobic and resistance) on blood glucose and incretin hormone that could control the diabetes in type 2 diabetes. dc.contributor.author: Alsubaie, Nawal; Alharbi, Bander; Sahota, T. S.; Taylor, M. Joan dc.description: open access journal
  • Low-Field, Benchtop NMR Spectroscopy as a Potential Tool for Point-of-Care Diagnostics of Metabolic Conditions: Validation, Protocols and Computational Models
    dc.title: Low-Field, Benchtop NMR Spectroscopy as a Potential Tool for Point-of-Care Diagnostics of Metabolic Conditions: Validation, Protocols and Computational Models dc.contributor.author: Percival, B.C.; Grootveld, M.; Gibson, M.; Osman, Y.; Molinari, M.; Jafari, F.; Sahota, T. S.; Martin, M.; Casanova, F.; Mather, M.L.; Edgar, M.; Masania, J.; Wilson, Philippe B. dc.description.abstract: Novel sensing technologies for liquid biopsies offer promising prospects for the early detection of metabolic conditions through omics techniques. Indeed, high-field nuclear magnetic resonance (NMR) facilities are routinely used for metabolomics investigations on a range of biofluids in order to rapidly recognise unusual metabolic patterns in patients suffering from a range of diseases. However, these techniques are restricted by the prohibitively large size and cost of such facilities, suggesting a possible role for smaller, low-field NMR instruments in biofluid analysis. Herein we describe selected biomolecule validation on a low-field benchtop NMR spectrometer (60 MHz), and present an associated protocol for the analysis of biofluids on compact NMR instruments. We successfully detect common markers of diabetic control at low-to-medium concentrations through optimised experiments, including α-glucose (≤2.8 mmol/L) and acetone (25 µmol/L), and additionally in readily accessible biofluids, particularly human urine. We present a combined protocol for the analysis of these biofluids with low-field NMR spectrometers for metabolomics applications, and offer a perspective on the future of this technique appealing to ‘point-of-care’ applications. dc.description: open access article
  • What effect does 6 weeks of moderate-intensity combined aerobic and resistance exercise have on the inflammatory nature of prediabetes subject?
    dc.title: What effect does 6 weeks of moderate-intensity combined aerobic and resistance exercise have on the inflammatory nature of prediabetes subject? dc.contributor.author: Al Harby, Bandar Manawer; Taylor, M. Joan; Sahota, T. S. dc.description.abstract: Introduction: Type-2 diabetes is a long-term metabolic disorder that considered as a disease of adulthood. It is often progression in different phases from normoglycemia phase to pre-diabetes phase and then incident T2D. In additions immune response involved in each phase of type-2 diabetes (T2D) development consider to be different. Physical exercise known to be effective strategy as primary prevention mechanism for people whom at risk to develop diabetes. However, the extent to which exercise has effect on the nature of immune response during pre-diabetes phase not fully understood. Purpose: The aim is to investigate what effect 6 weeks of moderate-intensity combined aerobic and resistance exercise has on the inflammatory nature of pre-diabetes subjects. Methods: Three groups of volunteers were involved in this study: ND, PRE-d and control. The ND and PRE-D volunteers participated in the main exercise trial which was a combined exercise session involving stretches, warm up on the bike for 10 min followed by 35 min of RE at 50-60% of 1RM. After RE they had 5 min of rest followed by 20 min of AE (cycling) at 50-60% of HRR and finally 10 min cooling down involves stretches. The exercise program involved 2 sessions (48 hours apart) for a total of 150 min each week for a 6-week period. Venous blood samples were collected from the volunteers in EDTA tubes. All blood samples were centrifuged at 3000 rpm for 15 min at 4 °C and stored in a -80 °C freezer until analysis by Randox machine. The primary outcome is to concentrate on metabolic results, such as improved HbA1c, blood pressure and improvements in insulin sensitivity determined by responses to oral glucose tolerance tests on independent days. The secondary outcome is change in serum level of inflammatory markers such interleukin 6 (IL-6), TNF-alpha, CRP and adiponectin. Results: There were significant reduction (p=0.00) on the HbA1c after applying of 6 weeks’ combination exercise intervention in both groups comparing to baseline. OGTT indicated significant differences between Pre Exercise and Post 12th exercise session in both groups with p=0.01. BG concentrations were reduced post each exercise session and was significant Post-EX S12 comparing PRE-EX to P=0.00 and P=0.09 in PRE-D and ND, respectively. SBP drops from 127.3±13.1 to 119.6±8.4 mmHg with P=0.04 in PRE-D while in ND was not significant. HR was significantly reduced (P=0.01) and goes from 73.5±10.3 to 70.3±12.1 in PRE-D and was significantly reduced (P=0.03). A significant improvement in interleukin 6, have been achieved with P=0.00 in PRE-D and wasn’t significant in ND group P=0.25. TNF-alpha no significant change has been achieved in all groups, while a significant improvement in adiponectin concentration PRE-D compare to ND and control groups. Conclusion: A combination exercise programs, which involves both RE and AE performed at moderate intensity (50-60% of 1RM) over 6-weeks period can improve overall inflammatory marker nature during pre-diabetes phase.
  • Thermoresponsive Gels
    dc.title: Thermoresponsive Gels dc.contributor.author: Taylor, M. Joan; Tomlins, P.; Sahota, T. S. dc.description.abstract: Thermoresponsive gelling materials constructed from natural and synthetic polymers can be used to provide triggered action and therefore customised products such as drug delivery and regenerative medicine types as well as for other industries. Some materials give Arrhenius-type viscosity changes based on coil to globule transitions. Others produce more counterintuitive responses to temperature change because of agglomeration induced by enthalpic or entropic drivers. Extensive covalent crosslinking superimposes complexity of response and the upper and lower critical solution temperatures can translate to critical volume temperatures for these swellable but insoluble gels. Their structure and volume response confer advantages for actuation though they lack robustness. Dynamic covalent bonding has created an intermediate category where shape moulding and self-healing variants are useful for several platforms. Developing synthesis methodology—for example, Reversible Addition Fragmentation chain Transfer (RAFT) and Atomic Transfer Radical Polymerisation (ATRP)—provides an almost infinite range of materials that can be used for many of these gelling systems. For those that self-assemble into micelle systems that can gel, the upper and lower critical solution temperatures (UCST and LCST) are analogous to those for simpler dispersible polymers. However, the tuned hydrophobic-hydrophilic balance plus the introduction of additional pH-sensitivity and, for instance, thermochromic response, open the potential for coupled mechanisms to create complex drug targeting effects at the cellular level. dc.description: An invited review and relates to the responsive gel used in the "artificial pancreas" work og INsmart, DMU. This article is an Open Access journal.
  • Closed-loop glycaemic control using an implantable artificial pancreas in diabetic domestic pig
    dc.title: Closed-loop glycaemic control using an implantable artificial pancreas in diabetic domestic pig dc.contributor.author: Taylor, M. Joan; Gregory, R.; Tomlins, P.; Jacob, D.; Hubble, J.; Sahota, T. S. dc.description.abstract: The performance of a completely implantable peritoneal artificial pancreas (AP) has been demonstrated in principle in a live diabetic domestic pig. The device consists of a smart glucose-sensitive gel that forms a gateway to an insulin reservoir and is designed to both sense glucose and deliver insulin in the peritoneal cavity. It can be refilled with insulin via subcutaneous ports and surgery was developed to insert the AP. Diabetes was induced with streptozotocin (STZ), the device filled with insulin (Humulin1 R U-500) in situ and the animal observed for several weeks, during which time there was normal access to food and water and several oral glucose challenges. Blood glucose (BG) levels were brought down from >30 mmol/L (540 mg/dL) to non-fasted values between 7 and 13 mmol/L (126–234 mg/dL) about five days after filling the device. Glucose challenge responses improved ultimately so that, starting at 10 mmol/L (180 mg/dL), the BG peak was 18 mmol/L (324 mg/dL) and fell to 7 mmol/L (126 mg/dL) after 30 min, contrasting with intravenous attempts. The reservoir solution was removed after 8 days of blood glucose levels during which they had been increasingly better controlled. A rapid return to diabetic BG levels (30 mmol/L) occurred only after a further 24 days implying some insulin had remained in the device after removal of the reservoir solution. Thus, the closed loop system appeared to have particular influence on the basal and bolus needs for the 8 days in which the reservoir solution was in place and substantial impact for a further 3 weeks. No additional insulin manual adjustment was given during this period. dc.description: INsmart in the DMU Pharmacy department in association with University Hospitals Leicester, Bath University, National Physical Laboratory and Renfrew International Group Leicester
  • Synthesis and Identification of FITC-Insulin Conjugates Produced Using Human Insulin and Insulin Analogues for Biomedical Applications
    dc.title: Synthesis and Identification of FITC-Insulin Conjugates Produced Using Human Insulin and Insulin Analogues for Biomedical Applications dc.contributor.author: Jacob, Dolly; Taylor, M. Joan; Tomlins, P.; Sahota, T. S. dc.description.abstract: fluorescein isothiocyanate (FITC) and the conjugate species produced were identified using high performance liquid chromatography and electrospray mass spectroscopy. Mono-labelled FITC-insulin conjugate (A1 or B1) was successfully produced using human insulin at short reaction times (up to 5 h) however the product always contained some unlabelled native human insulin. As the reaction time was increased over 45 h, no unlabelled native human insulin was present and more di-labelled FITC-insulin conjugate (A1B1) was produced than mono-labelled conjugate with the appearance of tri-labelled conjugate (A1B1B29) after 20 h reaction time. The quantities switch from mono-labelled to di-labelled FITC-insulin conjugate between reaction times 9 and 20 h. In the presence of phenol or m-cresol, there appears to be a 10 % decrease in the amount of mono-labelled conjugate and an increase in di-labelled conjugate produced at lower reaction times. Clinically used insulin analogues present in commercially available preparations were successfully fluorescently labelled for future biomedical applications. dc.description: We thank EPSRC National Mass Spectrometry Facility, Swansea University for their help with FITC-insulin analysis.

Click here for a full listing of Tarsem Sahota's publications and outputs.

Key research outputs

Taylor, M. J., S. Tanna, et al. (2008). "UV Cross-Linked Dextran Methacrylate - Concanavalin A Methacrylamide Gel Materials for Self-Regulated Insulin Delivery." Drug Dev Ind Pharm 34(1): 73-82.

Taylor M J, Tanna, S., Sahota, T. S. et al “Glucose-sensitive gel rheology of dextran-concanavalin A mixtures suitable for self-regulating insulin delivery” Pharmaceutical Development and Technology 15(1):80-8, 2010.

Taylor M J, Sahota, T. S. “In vivo study of a polymeric glucose sensitive insulin delivery system using a rat model” Journal of Pharmaceutical Sciences, 9, 10, 4215-4227 2010.

S., Sahota, Sawicka,  Taylor M J, Tanna, , T. S. “Effect of varying molecular weight of dextran on acrylic derivatised dextran and concanavalin A glucose-responsive materials for closed-loop insulin delivery” Drug Development and Industrial Pharmacy, 2011, Mar;37(3):351-8.

Research interests/expertise

  • Insulin physico-chemistry
  • Diabetes control
  • Drug delivery
  • Rheometry (viscosity of gels and sols)
  • Engineering and design of devices for drug delivery
  • Physiological parameters for exercise in diabetes.

Conference attendance

Posters
Taylor, M. & Sahota, T. Glucose-sensitive insulin delivery in vivo - an artificial pancreas? (Poster) 3rd International Conference on Advanced Treatments and Technologies (ATTD) Basel Feb 2010

Sahota T.S. & Taylor M.J. Competitive displacement of blue dextran by cibacron blue in dextran albumin gels? (Poster) Intern. Symp. Control. Rel. Bioact. Mater, Controlled Release Society, Inc. Portland, Oregon 2010

Sahota T.S. & Taylor M.J. Closed Loop Delivery in the Pig (accepted poster) Controlled Release Society Annual Symposium, Quebec, Canada 2012

Consultancy work

  • Polymer synthesis
  • Rheology
  • HPLC
  • Pressure measurements
  • Diabetes
  • Focus groups and survey design
  • GPC

Externally funded research grants information

Co-Investigator on the following grants:

  • NEAT funding (£278k)
  • HFCE matched funding (25k)
  • Edith Murphy Foundation 2008 (£50k)
  • Edith Murphy Foundation 2011 (£200k)
  • Lachesis (£5k)