Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Diabetologia
Published in: Diabetologia 7/2006

01-07-2006 | For Debate

Neel revisited: the adipocyte, seasonality and type 2 diabetes

Authors: E. M. Scott, P. J. Grant

Published in: Diabetologia | Issue 7/2006

Login to get access

Abstract

The modern epidemic of obesity and insulin resistance with cardiovascular risk factor clustering is related to the development of type 2 diabetes and cardiovascular disease. Over 40 years ago, Neel postulated that insulin resistance should confer survival benefit. Extrapolating Neel’s hypothesis, we propose that the cluster of associated abnormalities also confers survival benefit and is related to metabolic responses seen in seasonally responsive animals. Weight gain in preparation for winter is accompanied by a range of acute metabolic changes virtually identical to the long-term changes seen in type 2 diabetes. In seasonal animals the responses are acute, physiological and protective. In man, similar responses that would once have conferred survival benefit have become chronic, pathological and harmful in modern life. We hypothesise that type 2 diabetes and cardiovascular disease in man are the result of chronic and inappropriate pineal–hypothalamic–adipocyte interactions biologically related to seasonal change.
Literature
1.
2.
Stern MP (1995) Diabetes and cardiovascular disease. The ‘common soil’ hypothesis. Diabetes 44:369–374PubMedCrossRef
3.
Neel JV (1962) Diabetes mellitus: a ‘thrifty’ genotype rendered detrimental by ‘progress’? Am J Hum Genet 14:353–362PubMed
4.
Reaven GM (1988) Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37:1595–1607PubMedCrossRef
5.
Hsueh WA, Law R (2003) The central role of fat and effect of peroxisome proliferator-activated receptor-gamma on progression of insulin resistance and cardiovascular disease. Am J Cardiol 92:3J–9JPubMedCrossRef
6.
Matsuzawa Y, Funahashi T, Nakamura T (1999) Molecular mechanism of metabolic syndrome X: contribution of adipocytokines adipocyte-derived bioactive substances. Ann NY Acad Sci 892:146–154PubMedCrossRef
7.
Smith SA (2003) Central role of the adipocyte in the insulin-sensitising and cardiovascular risk modifying actions of the thiazolidinediones. Biochimie 85:1219–1230PubMedCrossRef
8.
Goldfine AB, Kahn CR (2003) Adiponectin: linking the fat cell to insulin sensitivity. Lancet 362:1431–1432PubMedCrossRef
9.
Sharma AM, Tarnopolsky MA (2005) Regulating adiponectin: of flax and flux. Diabetologia 48:1035–1037PubMedCrossRef
10.
Matsuzawa Y, Funahashi T, Kihara S, Shimomura I (2004) Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol 24:29–33PubMedCrossRef
11.
Kumada M, Kihara S, Sumitsuji S et al (2003) Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol 23:85–89PubMedCrossRef
12.
Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG (2000) Central nervous system control of food intake. Nature 404:661–671PubMed
13.
Zimmet P, Hodge A, Nicolson M et al (1996) Serum leptin concentration, obesity, and insulin resistance in Western Samoans: cross sectional study. BMJ 313:965–969PubMed
14.
Fasshauer M, Paschke R (2003) Regulation of adipocytokines and insulin resistance. Diabetologia 46:1594–1603PubMedCrossRef
15.
Green A, Dobias SB, Walters DJ, Brasier AR (1994) Tumor necrosis factor increases the rate of lipolysis in primary cultures of adipocytes without altering levels of hormone-sensitive lipase. Endocrinology 134:2581–2588PubMedCrossRef
16.
Suganami T, Nishida J, Ogawa Y (2005) A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha. Arterioscler Thromb Vasc Biol 25:2062–2068PubMedCrossRef
17.
Shimomura I, Funahashi T, Takahashi M et al (1996) Enhanced expression of PAI-1 in visceral fat: possible contributor to vascular disease in obesity. Nat Med 2:800–803PubMedCrossRef
18.
19.
Baron AD, Steinberg H, Brechtel G, Johnson A (1994) Skeletal muscle blood flow independently modulates insulin-mediated glucose uptake. Am J Physiol 266:E248–E253PubMed
20.
21.
Bartness TJ, Powers JB, Hastings MH, Bittman EL, Goldman BD (1993) The timed infusion paradigm for melatonin delivery: what has it taught us about the melatonin signal, its reception, and the photoperiodic control of seasonal responses? J Pineal Res 15:161–190PubMedCrossRef
22.
Cai D, McCarron RM, Yu EZ, Li Y, Hallenbeck J (2004) Akt phosphorylation and kinase activity are down-regulated during hibernation in the 13-lined ground squirrel. Brain Res 1014:14–21PubMedCrossRef
23.
Buck MJ, Squire TL, Andrews MT (2002) Coordinate expression of the PDK4 gene: a means of regulating fuel selection in a hibernating mammal. Physiol Genomics 8:5–13PubMed
24.
Tokuyama K, Galantino HL, Green R, Florant GL (1991) Seasonal glucose uptake in marmots (Marmota flaviventris): the role of pancreatic hormones. Comp Biochem Physiol A 100:925–930PubMedCrossRef
25.
Florant GL, Porst H, Peiffer A et al (2004) Fat-cell mass, serum leptin and adiponectin changes during weight gain and loss in yellow-bellied marmots (Marmota flaviventris). J Comp Physiol [B] 174:633–639
26.
Novoselova EG, Kolaeva SG, Makar VR, Agaphonova TA (2000) Production of tumor necrosis factor in cells of hibernating ground squirrels Citellus undulatus during annual cycle. Life Sci 67:1073–1080PubMedCrossRef
27.
Mominoki K, Tsuruga H, Morimatsu M, Saito M (1996) Seasonal variations of blood haptoglobin level of brown bears in Japan. Comp Biochem Physiol A Physiol 114:349–353PubMedCrossRef
28.
De Wit CA, Persson G, Nilsson IM, Johansson BW (1985) Circannual changes in blood coagulation factors and the effect of warfarin on the hedgehog Erinaceus europaeus. Comp Biochem Physiol A 80:43–47PubMedCrossRef
29.
Alonso-Vale MI, Andreotti S, Peres SB et al (2005) Melatonin enhances leptin expression by rat adipocytes in the presence of insulin. Am J Physiol Endocrinol Metab 288:E805–E812PubMedCrossRef
30.
Castex C, Tahri A, Hoo-Paris R, Sutter BC (1984) Hibernation depth influences the edible dormouse pancreatic B cell during the spring arousal. Gen Comp Endocrinol 54:123–131PubMedCrossRef
31.
Vitale PM, Darrow JM, Duncan MJ, Shustak CA, Goldman BD (1985) Effects of photoperiod, pinealectomy and castration on body weight and daily torpor in Djungarian hamsters (Phodopus sungorus). J Endocrinol 106:367–375PubMed
32.
Stehle JH, Von Gall C, Korf HW (2003) Melatonin: a clock-output, a clock-input. J Neuroendocrinol 15:383–389PubMedCrossRef
33.
Holzberg D, Albrecht U (2003) The circadian clock: a manager of biochemical processes within the organism. J Neuroendocrinol 15:339–343PubMedCrossRef
34.
Lincoln GA, Andersson H, Loudon A (2003) Clock genes in calendar cells as the basis of annual timekeeping in mammals—a unifying hypothesis. J Endocrinol 179:1–13PubMedCrossRef
35.
Ando H, Yanagihara H, Hayashi Y et al (2005) Rhythmic mRNA expression of clock genes and adipocytokines in mouse visceral adipose tissue. Endocrinology 146:5631–5636PubMedCrossRef
36.
Loudon AS, Curlewis JD (1988) Cycles of antler and testicular growth in an aseasonal tropical deer (Axis axis). J Reprod Fertil 83:729–738PubMedCrossRef
37.
Rudic RD, McNamara P, Curtis AM et al (2004) BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis. PLoS Biol 2:e377PubMedCrossRef
38.
Turek FW, Joshu C, Kohsaka A et al (2005) Obesity and metabolic syndrome in circadian Clock mutant mice. Science 308:1043–1045PubMedCrossRef
39.
Anhe GF, Caperuto LC, Pereira-Da-Silva M et al (2004) In vivo activation of insulin receptor tyrosine kinase by melatonin in the rat hypothalamus. J Neurochem 90:559–566PubMedCrossRef
40.
Lund J, Arendt J, Hampton SM, English J, Morgan LM (2001) Postprandial hormone and metabolic responses amongst shift workers in Antarctica. J Endocrinol 171:557–564PubMedCrossRef
41.
42.
Wehr TA (2001) Photoperiodism in humans and other primates: evidence and implications. J Biol Rhythms 16:348–364PubMedCrossRef
43.
Wehr TA, Giesen HA, Moul DE, Turner EH, Schwartz PJ (1995) Suppression of men’s responses to seasonal changes in day length by modern artificial lighting. Am J Physiol 269:R173–R178PubMed
44.
Nagaya T, Yoshida H, Takahashi H, Kawai M (2002) Markers of insulin resistance in day and shift workers aged 30–59 years. Int Arch Occup Environ Health 75:562–568PubMedCrossRef
45.
Karlsson BH, Knutsson AK, Lindahl BO, Alfredsson LS (2003) Metabolic disturbances in male workers with rotating three-shift work. Results of the WOLF study. Int Arch Occup Environ Health 76:424–430PubMedCrossRef
46.
Knutsson A (2003) Health disorders of shift workers. Occup Med (Lond) 53:103–108CrossRef
47.
Karlsson B, Alfredsson L, Knutsson A, Andersson E, Toren K (2005) Total mortality and cause-specific mortality of Swedish shift- and dayworkers in the pulp and paper industry in 1952–2001. Scand J Work Environ Health 31:30–35PubMed
48.
Knutsson A, Hallquist J, Reuterwall C, Theorell T, Akerstedt T (1999) Shiftwork and myocardial infarction: a case–control study. Occup Environ Med 56:46–50PubMedCrossRef
49.
Andrews MT (2004) Genes controlling the metabolic switch in hibernating mammals. Biochem Soc Trans 32:1021–1024PubMedCrossRef
Metadata
Title
Neel revisited: the adipocyte, seasonality and type 2 diabetes
Authors
E. M. Scott
P. J. Grant
Publication date
01-07-2006
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 7/2006
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-006-0280-x

Other articles of this Issue 7/2006

Diabetologia 7/2006 Go to the issue

Article

Human adipose triglyceride lipase (PNPLA2) is not regulated by obesity and exhibits low in vitro triglyceride hydrolase activity

Article

Adiponectin in human pregnancy: implications for regulation of glucose and lipid metabolism

Article

Genetic variation in the hepatic lipase gene and the risk of coronary heart disease among US diabetic men: potential interaction with obesity

Article

Common variants in MODY genes increase the risk of gestational diabetes mellitus

Article

Intracellular ATP-sensitive K+ channels in mouse pancreatic beta cells: against a role in organelle cation homeostasis

Article

Association of soluble CD40 ligand with carotid atherosclerosis in Japanese type 1 diabetic patients
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits