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Type 2 Diabetes

Research Lines:
1. Therapeutic potential of drugs targeting cannabinoid- and cannabinoid-like
receptors in obesity, prediabetes and type 2 diabetes
2. Phenolic compounds from Extra Virgin Olive Oil (EVOO) in preventing type 2 diabetes onset; molecular insights
3. Underlying molecular processes and crosstalk between signalling pathways
modulating inflammation and related processes during insulin resistance and
Summary of Research:
Type 2 Diabetes (T2D) is a chronic disease of high prevalence (around 13% in
the Spanish population) and increasing incidence that is linked to obesity
pandemic. A key hallmark of diabetes is high blood glucose level (hyperglycemia) that eventually leads to macro-vascular and micro-vascular complications notably decreasing life expectancy and quality of life in patients.
Underlying cellular processes leading to hyperglycemia are defective insulin
secretion and insulin resistance in target tissues. Emerging evidence suggest
that obesity-related inflammation (meta-inflammation) is a key factor involved in these alterations. Interestingly, cannabinoids and related compounds as well as polyphenols from EVOO display anti-inflammatory actions. Hence, we aim at better understand the role of these receptors in meta-inflammation and beta-cell failure during type 2 diabetes onset and to assess new cannabinoid- and
EVOO-based pharmacological and nutritional approaches in order to design
innovative treatments that improve health outcomes in daily clinical practice.


Fco. Javier Bermúdez-Silva
UGC Endocrinología y Nutrición. IBIMA.

Laboratorio de Investigación-Hormonas
Plaza del Hospital Civil s/n, Pabellón 2, sótano 29009, Malaga (Spain)


Ongoing and finished grants in the last five years

Study of polyphenols and terpenoids from extra virgin olive oil for the prevention and treatment of type 2 diabetes. Capacity of these compounds to modulate cannabinoid receptors.

INVESTIGADOR PRINCIPAL: Francisco Javier Bermúdez Silva

DURACIÓN: 2018-2020 PRESUPUESTO: 141,570€

FINANCIADO POR: FIS (Instituto de Salud Carlos III)

Beneficial actions of polyphenols from Extra Virgin Olive Oil in pancreatic islets and their potential in preventing type 2 diabetes.

INVESTIGADOR PRINCIPAL: Francisco Javier Bermúdez Silva 

DURACIÓN: 2017-2019 PRESUPUESTO: 52,445€

FINANCIADO POR: Servicio Andaluz de Salud

Targeting the Endocannabinoid System within Islets of Langerhans to Protect against Immune Destruction (DIRECtA)

INVESTIGADOR PRINCIPAL: Francisco Javier Bermúdez Silva

DURACIÓN: 2018-2019 PRESUPUESTO: 158,121.60€


Anti-inflammatory and anti-oxidant protection of pancreatic islets in type 2 diabetes. Synergism with pharmacological approaches boosting insulin secretion.

INVESTIGADOR PRINCIPAL: Francisco Javier Bermúdez Silva

DURACIÓN: 2014-2016 PRESUPUESTO: 115,555€

FINANCIADO POR: FIS (Instituto de Salud Carlos III)

Functional impact of synthetic cannabinoids in beta-cell proliferation in pancreatic islets. Putative applications in diabetes.

INVESTIGADOR PRINCIPAL: Silvana Yanina Romero Zerbo 

DURACIÓN: 2013-2015 PRESUPUESTO: 31,327€

FINANCIADO POR: Consejería de Salud Junta de Andalucía


Relevant Publications

Romero-Zerbo SY, García-Fernández M, Espinosa-Jiménez V, Pozo-Morales M, Escamilla-Sánchez A, Sánchez-Salido L, Lara E, Cobo-Vuilleumier N, Rafacho A, Olveira G, Rojo-Martínez G, Gauthier BR, González-Mariscal I, Bermúdez-Silva FJ. The Atypical Cannabinoid Abn-CBD Reduces Inflammation and Protects Liver, Pancreas, and Adipose Tissue in a Mouse Model of Prediabetes and Non-alcoholic Fatty Liver Disease. Front Endocrinol (Lausanne). 2020 Mar 6;11:103. doi: 10.3389/fendo.2020.00103. PMID: 32210914.
Cobo-Vuilleumier N, Lorenzo PI, Rodríguez NG, Herrera Gómez IG, Fuente-Martin E, López-Noriega L, Mellado-Gil JM, Romero-Zerbo SY, Baquié M, Lachaud CC, Stifter K, Perdomo G, Bugliani M, De Tata V, Bosco D, Parnaud G, Pozo D, Hmadcha A, Florido JP, Toscano MG, de Haan P, Schoonjans K, Sánchez Palazón L, Marchetti P, Schirmbeck R, Martín-Montalvo A, Meda P, Soria B, Bermúdez-Silva FJ, St-Onge L, Gauthier BR. LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus. Nat Commun. 2018 Apr 16;9(1):1488. doi: 10.1038/s41467-018-03943-0. PMID: 29662071.
Ruz-Maldonado I, Pingitore A, Liu B, Atanes P, Huang GC, Baker D, Alonso FJ, Bermúdez-Silva FJ, Persaud SJ. LH-21 and Abn-CBD improve β-cell function in isolated human and mouse islets through GPR55-dependent and -independent signalling. Diabetes Obes Metab. 2018 Apr;20(4):930-942. doi: 10.1111/dom.13180. Epub 2018 Jan 10. PMID: 29205751
Romero-Zerbo SY, Ruz-Maldonado I, Espinosa-Jiménez V, Rafacho A, Gómez-Conde AI, Sánchez-Salido L, Cobo-Vuilleumier N, Gauthier BR, Tinahones FJ, Persaud SJ, Bermúdez-Silva FJ. The cannabinoid ligand LH-21 reduces anxiety and improves glucose handling in diet-induced obese pre-diabetic mice. Sci Rep. 2017, Jun 21;7(1):3946. doi: 10.1038/s41598-017-03292-w.
Bermudez-Silva FJ, Romero-Zerbo SY, Haissaguerre M,  Ruz-Maldonado I, Lhamyani S, El Bekay R, Tabarin A, Marsicano G, Cota D. Cannabinoid CB1 receptors and mTORC1 signalling pathway interact to modulate glucose homeostasis. Disease Models & Mechanisms 2016, Jan; 9(1):51-61. doi: 10.1242/dmm.020750.
Romero-Zerbo SY, Bermúdez-Silva FJ. Cannabinoids, eating behaviour and energy homeostasis. Drug Test Anal 2014, Jan; 6(1-2):52-8. doi: 10.1002/dta.1594.
Romero-Zerbo SY, Garcia-Gutierrez MS, Suárez J, Rivera P, Vida M, Rodriguez de Fonseca F, Manzanares J, Bermudez-Silva FJ. Overexpression of cannabinoid CB2 receptor in the brain induces hyperglycaemia and a lean phenotype in adult mice. J Neuroendocrinology 2012, Aug;24(8):1106-19

Romero-Zerbo SY, Rafacho A, Díaz-Arteaga A, Suárez J, Quesada I, Ross RA, Dieguez C, Rodríguez De Fonseca F, Nogueiras R, Nadal A, Bermúdez-Silva FJ. A role for the putative cannabinoid receptor GPR55 in the islets of Langerhans. J Endocrinol 2011, Nov; 211(2):177-85
Bermudez-Silva FJ, Viveros MP, McPartland JM, de Fonseca FR. The endocannabinoid system, eating behavior and energy homeostasis: The end or a new beginning? Pharmacol Biochem Behav. 2010 Jun; 95:375-82
Bermúdez-Silva FJ, Suárez J, Baixeras E, Cobo N, Bautista D, Cuesta-Muñoz AL, Fuentes E, Juan-Pico P, Castro MJ, Nadal A and Rodríguez de Fonseca F.  Presence of functional cannabinoid receptors in human endocrine pancreas (2008) Diabetologia 51(3):476-87

Available Techniques

– Mouse models of high-fat-diet-induced obesity, prediabetes and type 2 diabetes
– Metabolic assessment of the effects of drugs and food supplements in animal models of obesity, pre-diabetes and type 2 diabetes
– Analysis of inflammatory and oxidative processes in animal models
– Mouse models for the study of the cannabinoid type 1 receptor (CB1R): Global CB1R knockout mice and inducible beta cell-specific CB1R knockout mice (MIP-Cre CNR1 LoxP/LoxP )
– Isolation of mouse islets of Langerhans and ex vivo experiments in human and mouse isolated islets (insulin and glucagon secretion, viability, apoptosis, proliferation)
– In vitro experiments in beta cell lines (MIN-6)
– Protein expression by Immunohistochemistry, immunocytochemistry,
immunofluorescence and Western Blot
– Quantification of gene expression by RT qPCR
– Quantification of hormones and cytokines by ELISA and multiplex assays in serum/plasma and cell/tissue extracts
– Nutritional Intervention clinical trials