Overview
Ana Cruz moved from Portugal to the UK in 2010 to complete her degree in Biological Sciences (Biomolecular stream) at the University of Reading (2014). A keen interest in skeletal muscle physiology led her to pursue a research Masters degree in Biomedical Research (2014/15) which she undertook under the supervision of Dr. Keith Foster and during which she investigated pharmacological approaches to treat Duchenne Muscular Dystrophy. The passion for understanding muscle physiology in disease grew and led Ana to seek a PhD at Exeter University under the supervision of Dr. Craig Beall and Dr. Benjamin Wall. Shortly before starting her PhD, Ana dipped her toes in another of her fields of interest, Neuroscience, by undertaking a short Postgraduate qualification in “Fundamental of Neuroscience” at the University of Minho. The combined interest in central and peripheral regulation of health and disease led Ana to complete her PhD at Exeter, which focused on investigating the signalling and molecular mechanisms that regulate whole energy metabolism and glucose homeostasis in diabetes.
The interest in energy metabolism and glucose homeostasis is ongoing as Ana continues to investigate how activation of energy sensors in the brain may help amplify the physiological response to hypoglycaemia as well as how glucose clearance into metabolically active tissues can be recovered in insulin resistant states. The outcomes of this research will hopefully contribute to the treatment of both Type 1 and Type 2 diabetes, which is one of Ana’s major career goals.
Outside the lab (the few remaining hours) Ana enjoys exercising (lifting heavy weights or group circuits), cooking and crocheting, all of which can be followed by a social visit to the pub.
Follow @AnaMiguelCruz on twitter for science updates and more
Qualifications
- PhD Medical Studies
- MRes Biomedical Research - Distinction
- BSc (Hons) Biological Sciences – First Class
Links
Twitter: @AnaMiguelCruz
Research Gate: https://www.researchgate.net/profile/Ana_Cruz14
ORCID ID: 0000-0002-9290-6752
Google scholar: https://scholar.google.com/citations?hl=en&user=XDUduE8AAAAJ&view_op=list_works&gmla=AJsN-F5L4E_yeS8pQ-FB1qmyBqVP1BAUoozR5-HMwhl_ZBSQqUFtKzSYwZanaMI2ICSfCQ1PF15emYwlOpYM6SwiWb72K0loAjO89gj6cYgxKkBidkfisyU
Research
Research interests
Dr. Ana Cruz is primarily interested in understanding how the body regulates its energy needs and how this is altered in disease. Controlling energy substrates, such as blood sugar, remains a challenge for individuals with diabetes. Ana’s research focuses on understanding the molecular mechanisms that control blood glucose, particularly the involvement of the brain and muscle in this regulation and how these can be therapeutically targeted to treat diabetes.
Ana is a member of the Beall lab, whose research interests focus on the integrated physiology of glucose homeostasis in both Type 1 and Type 2 diabetes. Lab members range from undergraduates to postdoctoral fellows and projects are currently focusing on regulation of pancreatic alpha cell function, brain-pancreas communication, neural regulation of hepatic glucose production and skeletal muscle anabolic signaling.
Techniques
- Cannulation/Venipuncture
- Glucose clamping
- In vivo metabolic physiology
- Western blotting
- Live-cell imaging
- Enzyme assays
- Calcium imaging
- Amino acid tracer technology
Research projects
- Does an orally active brain permeable AMPK activator amplify the counterregulatory response to hypoglycaemia
- Control of skeletal muscle glucose metabolism by the purinergic signaling system
- Mechanisms underlying skeletal muscle insulin and anabolic resistance
Grants/Funding:
- Nov 2019: The British Society for Neuroendocrinology travel grant
- May 2019: The Physiological Society travel grant
- Mar 2019: Diabetes UK Conference travel grant
- Sep 2018–ongoing: Northcott Devon Medical Foundation- Characterising purinergic control of skeletal muscle mTOR pathway activity; Co-investigator
- Mar 2018: Diabetes UK Conference travel grant
Publications
Key publications | Publications by category | Publications by year
Publications by category
Journal articles
Vlachaki Walker JM, Robb JL, Cruz AM, Malhi A, Weightman Potter PG, Ashford ML, McCrimmon RJ, Ellacott KL, Beall C (In Press). AMP-activated protein kinase activator A-769662 increases intracellular calcium and ATP release from astrocytes in an AMPK-independent manner.
Diabetes, Obesity and Metabolism Full text.
Cruz AM, Malekizadeh Y, Vlachaki Walker JM, Weightman Potter PG, Pye K, Shaw SJ, Ellacott KLJ, Beall C (In Press). Brain permeable AMPK activator R481 raises glycemia by autonomic nervous system activation and amplifies the counterregulatory response to hypoglycemia in rats.
Abstract:
Brain permeable AMPK activator R481 raises glycemia by autonomic nervous system activation and amplifies the counterregulatory response to hypoglycemia in rats
ABSTRACTAMP-activated protein kinase (AMPK) is a critical cellular and whole body energy sensor activated by energy stress, including hypoglycemia, which is frequently experienced by people with diabetes. Previous studies using direct delivery of an AMPK activator to the ventromedial hypothalamus (VMH) in rodents increased hepatic glucose production. Moreover, recurrent glucoprivation in the hypothalamus leads to blunted AMPK activation and defective hormonal responses to subsequent hypoglycemia. These data suggest that amplifying AMPK activation may prevent or reduce frequency hypoglycemia in diabetes. We used a novel brain-permeable AMPK activator, R481, which potently increased AMPK phosphorylation in vitro. R481 significantly increased peak glucose levels during glucose tolerance tests in rats, which were attenuated by treatment with AMPK inhibitor SBI-0206965 and completely abolished by blockade of the autonomic nervous system. This occurred without altering insulin sensitivity measured by hyperinsulinemic-euglycemic clamps. Endogenous insulin secretion was not altered by R481 treatment. During hyperinsulinemic-hypoglycemic clamp studies, R481 treatment reduced exogenous glucose requirements and amplified peak glucagon levels during hypoglycemia. These data demonstrate that peripheral administration of the brain permeable AMPK activator R481 amplifies the counterregulatory response to hypoglycemia in rats, which could have clinical relevance for prevention of hypoglycemia.
Abstract.
Wall BT, Cruz AM, Otten B, Dunlop MV, Fulford J, Porter C, Abdelrahman DR, Stephens FB, Dirks ML (2020). The Impact of Disuse and High-Fat Overfeeding on Forearm Muscle Amino Acid Metabolism in Humans.
The Journal of Clinical Endocrinology & Metabolism,
105(7).
Abstract:
The Impact of Disuse and High-Fat Overfeeding on Forearm Muscle Amino Acid Metabolism in Humans
Abstract
.
. Context
. Anabolic resistance is mechanistically implicated in muscle disuse atrophy.
.
.
. Objective
. The objective of this study is to assess whether anabolic resistance is associated with reduced postprandial amino acid uptake or exacerbated by excess lipid availability.
.
.
. Design, Setting, Participants, and Interventions
. Twenty men underwent 7 days of forearm immobilization while consuming a eucaloric (CON; n = 11) or high-fat overfeeding (HFD; n = 9; 50% excess energy as fat) diet (parallel design) within our Nutritional Physiology Research Unit.
.
.
. Main Outcome Measures
. Preimmobilization and postimmobilization we measured forearm muscle cross-sectional area (aCSA), and postabsorptive and postprandial (3-hour postingestion of a liquid, protein-rich, mixed meal) forearm amino acid metabolism using the arterialized venous-deep venous balance method and infusions of L-[ring-2H5]phenylalanine and L-[1-13C]leucine.
.
.
. Results
. Immobilization did not affect forearm muscle aCSA in either group, but tended to reduce postabsorptive phenylalanine (P =. 07) and leucine (P =. 05) net balances equivalently in CON and HFD. Mixed-meal ingestion switched phenylalanine and leucine net balances from negative to positive (P <. 05), an effect blunted by immobilization (P <. 05) and to a greater extent in HFD than CON (P <. 05). Preimmobilization, meal ingestion increased leucine rates of disappearance (Rd; P <. 05), with values peaking at 191% (from 87 ± 38 to 254 ± 60 µmol·min–1·100 mL forearm volume–1) and 183% (from 141 ± 24 to 339 ± 51 µmol·min–1·100 mL–1) above postabsorptive rates in CON and HFD, respectively, with meal-induced increases not evident postimmobilization in either group (P >. 05).
.
.
. Conclusions
. Disuse impairs the ability of a protein-rich meal to promote positive muscle amino acid balance, which is aggravated by dietary lipid oversupply. Moreover, disuse reduced postprandial forearm amino acid uptake; however, this is not worsened under high-fat conditions.
.
Abstract.
Full text.
Dirks ML, Wall BT, Otten B, Cruz AM, Dunlop MV, Barker AR, Stephens FB (2019). High-fat Overfeeding Does Not Exacerbate Rapid Changes in Forearm Glucose and Fatty Acid Balance During Immobilization.
The Journal of Clinical Endocrinology & Metabolism,
105(1), 276-289.
Abstract:
High-fat Overfeeding Does Not Exacerbate Rapid Changes in Forearm Glucose and Fatty Acid Balance During Immobilization
Abstract
.
. Context
. Physical inactivity and high-fat overfeeding have been shown to independently induce insulin resistance.
.
.
. Objective
. Establish the contribution of muscle disuse and lipid availability to the development of inactivity-induced insulin resistance.
.
.
. Design, Setting, Participants, and Interventions
. 20 healthy males underwent 7 days of forearm cast immobilization combined with a fully controlled eucaloric diet (n = 10, age 23 ± 2 yr, body mass index [BMI] 23.8 ± 1.0 kg·m-2) or a high-fat diet (HFD) providing 50% excess energy from fat (high-fat diet, n = 10, age 23 ± 2 yr, BMI 22.4 ± 0.8 kg·m-2).
.
.
. Main Outcome Measures
. Prior to casting and following 2 and 7 days of immobilization, forearm glucose uptake (FGU) and nonesterified fatty acid (NEFA) balance were assessed using the arterialized venous–deep venous (AV-V) forearm balance method following ingestion of a mixed macronutrient drink.
.
.
. Results
. 7 days of HFD increased body weight by 0.9 ± 0.2 kg (P = 0.002), but did not alter fasting, arterialized whole-blood glucose and serum insulin concentrations or the associated homeostatic model assessment of insulin resistance or Matsuda indices. Two and 7 days of forearm immobilization led to a 40 ± 7% and 52 ± 7% decrease in FGU, respectively (P < 0.001), with no difference between day 2 and 7 and no effect of HFD. Forearm NEFA balance tended to increase following 2 and 7 days of immobilization (P = 0.095).
.
.
. Conclusions
. Forearm immobilization leads to a rapid and substantial decrease in FGU, which is accompanied by an increase in forearm NEFA balance but is not exacerbated by excess dietary fat intake. Altogether, our data suggest that disuse-induced insulin resistance of glucose metabolism occurs as a physiological adaptation in response to the removal of muscle contraction.
.
Abstract.
Full text.
Conferences
Cruz AM, Malekizadeh Y, Walker JMV, Shaw S, Ellacott KLJ, Beall C (2019). AMP-activated protein kinase (AMPK) activator R481 improves the counterregulatory response to hypoglycaemia by amplifying glucagon release in healthy rats.
Author URL.
Cruz AML, Malekizadeh Y, Vlachaki Walker J, Ellacott K, Shaw S, Beall C (2019). Amplified Glucagon Response to Hypoglycemia following AMP-Activated Protein Kinase (AMPK) Activator R481 Treatment in Healthy Rats. American Diabetes Association. 7th - 11th Jun 2019.
Abstract:
Amplified Glucagon Response to Hypoglycemia following AMP-Activated Protein Kinase (AMPK) Activator R481 Treatment in Healthy Rats
Abstract.
Potter PGW, Cruz JMV, Cruz AM, Williamson R, Randall A, Beall C (2017). Human astrocytes are altered following chronic glucose variation: differential regulation of cytokine release and increased basal metabolism.
Author URL.
Publications by year
In Press
Vlachaki Walker JM, Robb JL, Cruz AM, Malhi A, Weightman Potter PG, Ashford ML, McCrimmon RJ, Ellacott KL, Beall C (In Press). AMP-activated protein kinase activator A-769662 increases intracellular calcium and ATP release from astrocytes in an AMPK-independent manner.
Diabetes, Obesity and Metabolism Full text.
Cruz AM, Malekizadeh Y, Vlachaki Walker JM, Weightman Potter PG, Pye K, Shaw SJ, Ellacott KLJ, Beall C (In Press). Brain permeable AMPK activator R481 raises glycemia by autonomic nervous system activation and amplifies the counterregulatory response to hypoglycemia in rats.
Abstract:
Brain permeable AMPK activator R481 raises glycemia by autonomic nervous system activation and amplifies the counterregulatory response to hypoglycemia in rats
ABSTRACTAMP-activated protein kinase (AMPK) is a critical cellular and whole body energy sensor activated by energy stress, including hypoglycemia, which is frequently experienced by people with diabetes. Previous studies using direct delivery of an AMPK activator to the ventromedial hypothalamus (VMH) in rodents increased hepatic glucose production. Moreover, recurrent glucoprivation in the hypothalamus leads to blunted AMPK activation and defective hormonal responses to subsequent hypoglycemia. These data suggest that amplifying AMPK activation may prevent or reduce frequency hypoglycemia in diabetes. We used a novel brain-permeable AMPK activator, R481, which potently increased AMPK phosphorylation in vitro. R481 significantly increased peak glucose levels during glucose tolerance tests in rats, which were attenuated by treatment with AMPK inhibitor SBI-0206965 and completely abolished by blockade of the autonomic nervous system. This occurred without altering insulin sensitivity measured by hyperinsulinemic-euglycemic clamps. Endogenous insulin secretion was not altered by R481 treatment. During hyperinsulinemic-hypoglycemic clamp studies, R481 treatment reduced exogenous glucose requirements and amplified peak glucagon levels during hypoglycemia. These data demonstrate that peripheral administration of the brain permeable AMPK activator R481 amplifies the counterregulatory response to hypoglycemia in rats, which could have clinical relevance for prevention of hypoglycemia.
Abstract.
2020
Wall BT, Cruz AM, Otten B, Dunlop MV, Fulford J, Porter C, Abdelrahman DR, Stephens FB, Dirks ML (2020). The Impact of Disuse and High-Fat Overfeeding on Forearm Muscle Amino Acid Metabolism in Humans.
The Journal of Clinical Endocrinology & Metabolism,
105(7).
Abstract:
The Impact of Disuse and High-Fat Overfeeding on Forearm Muscle Amino Acid Metabolism in Humans
Abstract
.
. Context
. Anabolic resistance is mechanistically implicated in muscle disuse atrophy.
.
.
. Objective
. The objective of this study is to assess whether anabolic resistance is associated with reduced postprandial amino acid uptake or exacerbated by excess lipid availability.
.
.
. Design, Setting, Participants, and Interventions
. Twenty men underwent 7 days of forearm immobilization while consuming a eucaloric (CON; n = 11) or high-fat overfeeding (HFD; n = 9; 50% excess energy as fat) diet (parallel design) within our Nutritional Physiology Research Unit.
.
.
. Main Outcome Measures
. Preimmobilization and postimmobilization we measured forearm muscle cross-sectional area (aCSA), and postabsorptive and postprandial (3-hour postingestion of a liquid, protein-rich, mixed meal) forearm amino acid metabolism using the arterialized venous-deep venous balance method and infusions of L-[ring-2H5]phenylalanine and L-[1-13C]leucine.
.
.
. Results
. Immobilization did not affect forearm muscle aCSA in either group, but tended to reduce postabsorptive phenylalanine (P =. 07) and leucine (P =. 05) net balances equivalently in CON and HFD. Mixed-meal ingestion switched phenylalanine and leucine net balances from negative to positive (P <. 05), an effect blunted by immobilization (P <. 05) and to a greater extent in HFD than CON (P <. 05). Preimmobilization, meal ingestion increased leucine rates of disappearance (Rd; P <. 05), with values peaking at 191% (from 87 ± 38 to 254 ± 60 µmol·min–1·100 mL forearm volume–1) and 183% (from 141 ± 24 to 339 ± 51 µmol·min–1·100 mL–1) above postabsorptive rates in CON and HFD, respectively, with meal-induced increases not evident postimmobilization in either group (P >. 05).
.
.
. Conclusions
. Disuse impairs the ability of a protein-rich meal to promote positive muscle amino acid balance, which is aggravated by dietary lipid oversupply. Moreover, disuse reduced postprandial forearm amino acid uptake; however, this is not worsened under high-fat conditions.
.
Abstract.
Full text.
2019
Cruz AM, Malekizadeh Y, Walker JMV, Shaw S, Ellacott KLJ, Beall C (2019). AMP-activated protein kinase (AMPK) activator R481 improves the counterregulatory response to hypoglycaemia by amplifying glucagon release in healthy rats.
Author URL.
Cruz AML, Malekizadeh Y, Vlachaki Walker J, Ellacott K, Shaw S, Beall C (2019). Amplified Glucagon Response to Hypoglycemia following AMP-Activated Protein Kinase (AMPK) Activator R481 Treatment in Healthy Rats. American Diabetes Association. 7th - 11th Jun 2019.
Abstract:
Amplified Glucagon Response to Hypoglycemia following AMP-Activated Protein Kinase (AMPK) Activator R481 Treatment in Healthy Rats
Abstract.
Dirks ML, Wall BT, Otten B, Cruz AM, Dunlop MV, Barker AR, Stephens FB (2019). High-fat Overfeeding Does Not Exacerbate Rapid Changes in Forearm Glucose and Fatty Acid Balance During Immobilization.
The Journal of Clinical Endocrinology & Metabolism,
105(1), 276-289.
Abstract:
High-fat Overfeeding Does Not Exacerbate Rapid Changes in Forearm Glucose and Fatty Acid Balance During Immobilization
Abstract
.
. Context
. Physical inactivity and high-fat overfeeding have been shown to independently induce insulin resistance.
.
.
. Objective
. Establish the contribution of muscle disuse and lipid availability to the development of inactivity-induced insulin resistance.
.
.
. Design, Setting, Participants, and Interventions
. 20 healthy males underwent 7 days of forearm cast immobilization combined with a fully controlled eucaloric diet (n = 10, age 23 ± 2 yr, body mass index [BMI] 23.8 ± 1.0 kg·m-2) or a high-fat diet (HFD) providing 50% excess energy from fat (high-fat diet, n = 10, age 23 ± 2 yr, BMI 22.4 ± 0.8 kg·m-2).
.
.
. Main Outcome Measures
. Prior to casting and following 2 and 7 days of immobilization, forearm glucose uptake (FGU) and nonesterified fatty acid (NEFA) balance were assessed using the arterialized venous–deep venous (AV-V) forearm balance method following ingestion of a mixed macronutrient drink.
.
.
. Results
. 7 days of HFD increased body weight by 0.9 ± 0.2 kg (P = 0.002), but did not alter fasting, arterialized whole-blood glucose and serum insulin concentrations or the associated homeostatic model assessment of insulin resistance or Matsuda indices. Two and 7 days of forearm immobilization led to a 40 ± 7% and 52 ± 7% decrease in FGU, respectively (P < 0.001), with no difference between day 2 and 7 and no effect of HFD. Forearm NEFA balance tended to increase following 2 and 7 days of immobilization (P = 0.095).
.
.
. Conclusions
. Forearm immobilization leads to a rapid and substantial decrease in FGU, which is accompanied by an increase in forearm NEFA balance but is not exacerbated by excess dietary fat intake. Altogether, our data suggest that disuse-induced insulin resistance of glucose metabolism occurs as a physiological adaptation in response to the removal of muscle contraction.
.
Abstract.
Full text.
2017
Potter PGW, Cruz JMV, Cruz AM, Williamson R, Randall A, Beall C (2017). Human astrocytes are altered following chronic glucose variation: differential regulation of cytokine release and increased basal metabolism.
Author URL.
Ana_MiguelCruz Details from cache as at 2020-06-04 08:13:59
Refresh publications
External Engagement and Impact
Awards
- July 2019: Above and Beyond award for Ambition: University of Exeter
- May 2016: University of Exeter, Postgraduate Annual research event, 1st Prize oral presentation
- 2014: Society for Endocrinology Undergraduate Achievement Award
Conferences and invited presentations
- Cruz, A.M., Malekizadeh, Y.M-Vlachaki Walker, J.M., Weightman Potter, P., Pye, K., Shaw., S., Ellacott., K.L.J., Beall., C. Metformin-like brain permeable AMPK activator R481 activates the autonomic nervous system to raise glycaemia without altering insulin sensitivity. Oral and poster presentation. Neuroscience of Energy Balance, Manchester, 2019
- Cruz, A.M., Malekizadeh, Y.M-Vlachaki Walker., J.M., Shaw., S., Ellacott., K.L.J., Beall., C. Amplified glucagon response to hypoglycaemia following AMP-activated protein kinase (AMPK) activator R481 treatments in healthy rats. Oral presentation. American Diabetes Association, San Francisco, 2019
-
- Cruz, A.M., Malekizadeh, Y.M-Vlachaki Walker, J.M., Shaw., S., Ellacott., K.L.J., Beall., C. AMP-activated protein kinase (AMPK) activator R481 improves the counter-regulatory response to hypoglycaemia by amplifying glucagon release in healthy rats. Poster presenting author, Diabetes UK Professional Conference, Liverpool, 2019
- Weightman Potter., P.G., Vlachaki Walker., J.M., Cruz., A.M., Williamson., R., Randall, A., Beall., C. – Human Primary Astrocyte (HPA) Metabolism is Altered Following Exposure to Recurrent Hypoglycaemia In Vitro – contributing author oral and poster presentation - American Diabetes Association, San Diego, 2017
- Weightman Potter., P.G., Vlachaki Walker., J.M., Cruz., A.M., Williamson., R., Randall, A., Beall., C. – Human astrocytes are altered following chronic glucose variation: Differential regulation of cytokine release and increased basal metabolism – contributing author poster presentation - Diabetes UK Professional Conference, Manchester, 2017
Presentations/Public engagement
- 10th March 2020: “I’m a Neuroscientist: Ask me anything” Brain awareness week, Exeter, invited speaker
- 30th July 2019: Exeter, Neuroscience Seminar series: Central regulation of glucose homeostasis by AMPK manipulation, invited speaker.
- 12th May 2017: Pint of Science, Exeter, Diet and inactivity on muscle function, invited speaker
- 6th Apr 2017: South Devon Diabetes UK patient group; Diet and inactivity on muscle function, invited speaker
- 16th Nov 2016: University of Exeter, IBCS seminar series; Fatty acid induced muscle anabolic resistance, invited speaker
