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“Developing and Nurturing a Career in GI Research” M. Michael Wolfe, M.D. Professor of Medicine

“Developing and Nurturing a Career in GI Research” M. Michael Wolfe, M.D. Professor of Medicine Research Professor of Physiology and Biophysics Boston University School of Medicine Chief, Section of Gastroenterology, Boston Medical Center. CAREER OPTIONS IN GI. Private practice

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“Developing and Nurturing a Career in GI Research” M. Michael Wolfe, M.D. Professor of Medicine

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  1. “Developing and Nurturing a Career in GI Research” M. Michael Wolfe, M.D. Professor of Medicine Research Professor of Physiology and Biophysics Boston University School of Medicine Chief, Section of Gastroenterology, Boston Medical Center

  2. CAREER OPTIONS IN GI • Private practice • Pharmaceutical industry • Academia Clinician-educator Clinical research Basic research Administration Miscellaneous

  3. PRIVATE PRACTICE Advantages Autonomy Financial Satisfaction Disadvantages Intellectual Insecurity “Pure” business Lack of esprit No mobility

  4. PHARMACEUTICAL INDUSTRY Advantages Exciting Translational Financial Upward mobility Satisfaction Disadvantages Intellectual Insecurity “Pure” business Goal-oriented No autonomy

  5. BASIC RESEARCH Advantages Intellectual Translational Autonomy Upward mobility Satisfaction Contribution to humankind Disadvantages Challenging Frustration Financial Grant dependence

  6. BASIC RESEARCH Advantages Intellectual Translational Autonomy Upward mobility Satisfaction Contribution to humankind Disadvantages Challenging Frustration Financial Grant dependence

  7. CONTRIBUTION TO HUMANKIND Lives Affected Clinician

  8. CONTRIBUTION TO HUMANKIND Lives Affected Clinician Educator

  9. CONTRIBUTION TO HUMANKIND Lives Affected Researcher

  10. OBESITY IN THE U.S. • Epidemiology 61% of adults are overweight (2000) 27% of adults are obese 14% of children are obese • Annual mortality due to obesity - 300,000* • Expenditures $300 billion $45 billion (consumer) on weight loss products * 450,000 due to tobacco (comparison)

  11. INSULIN IS AN EFFICIENCY HORMONE Insulin is the most potent anabolic hormone known, and promotes the synthesis and storage of carbohydrates, lipids and proteins, while inhibiting their degradation and release into the circulation. Saltiel AR and Kahn CR. Nature 2001;414:799-806.

  12. INCRETIN Conceptual hormone mediating the enteroinsular axis; released from small intestine by glucose-containing meals and stimulates the release of insulin from pancreatic b-islet cells

  13. EFFECTS OF ORAL AND IV GLUCOSE ON PLASMA INSULIN AND GLUCOSE McIntyre N et al. Lancet 1964;2:20-21.

  14. EFFECTS OF ORAL AND IV GLUCOSE ON PLASMA INSULIN AND GLUCOSE McIntyre N et al. Lancet 1964;2:20-21.

  15. * * 80 70 60 ** 50 40 30 20 10 0 Basal 0.9% NaCl ANTGIP GIP GIP GIP 0.5 1.0 1.5 1.5 GIP + ANTGIP EFFECT OF ANTGIP ON GIP-STIMULATED INSULIN RELEASE PLASMA INSULIN (mIU/ml) CONDITION Tseng C-C et al. J Clin Invest 1996;98:2440-5.

  16. ANTGIP No ANTGIP EFFECT OF ANTGIP ON PLASMA INSULIN AND SERUM GLUCOSE LEVELS * * N I 6 0 L U 5 0 S ) l N 4 0 m I / A 3 0 U I M m 2 0 ( S A 1 0 L P 0 0 1 0 2 0 3 0 4 0 T I M E ( m i n ) Tseng C-C et al. J Clin Invest 1996;98:2440-5.

  17. ANTGIP No ANTGIP EFFECT OF ANTGIP ON PLASMA INSULIN AND SERUM GLUCOSE LEVELS * * N I 6 0 L U 5 0 S ) l N 4 0 m I / A 3 0 U I M m 2 0 ( S A 1 0 L P 0 E 1 6 0 S O C 1 4 0 ) U l L m 1 2 0 / G g m M ( 1 0 0 U R E 8 0 S 0 1 0 2 0 3 0 4 0 T I M E ( m i n ) Tseng C-C et al. J Clin Invest 1996;98:2440-5.

  18. EFFECTS OF ANTGIP ON D-GLUCOSEABSORPTION FROM THE SMALL INTESTINE * AUC (mmol/min/g dry wt) Tseng C-C et al. Am J Physiol 1999;276:E1049-54.

  19. Gut glucose absorption Insulin release GIP “Overnutrition” Storage of fat GIP Antagonist

  20. EFFECT OF HIGH-FAT DIET ON BODYWEIGHT IN GIPR+/+ AND GIPR-/- MICE Miyawaki K et al. Nat Med 2002;8:738-42.

  21. EFFECT OF HIGH-FAT DIET ON BODYWEIGHT IN GIPR+/+ AND GIPR-/- MICE Miyawaki K et al. Nat Med 2002;8:738-42.

  22. GIPR+/+ GIPR-/- Miyawaki K et al. Nat Med 2002;8:738-42.

  23. WEIGHT LOSS SURGERY Gastric Bypass

  24. WEIGHT LOSS SURGERY K-cells (GIP containing) Gastric Bypass

  25. PEPTIDE LEVELS FOLLOWING GASTRIC BYPASS SURGERY 500 P = 0.09 P = 0.009 400 P = 0.003 300 PEPTIDE LEVELS (per ml) 200 GIP (pg/ml) GLP-1 (pmol/ml) 100 0 Insulin (mU/ml) -100 0 2 4 6 8 10 12 Insulin  by 33%, P=NS; C-peptide  by 29%, P = 0.019; Glucose: 129.3  99.1 n = 20 Weeks Clements RH et al. Amer Surg 2004;70:1-5.

  26. CONTRIBUTION TO HUMANKIND Lives Affected Researcher

  27. OBESITY AND TYPE 2 DIABETES A Progressive Problem Metabolic syndrome Normal Weight loss 47 M** Type 2 Oral Agents 5.9 M* b-cellfunction Type 1 Failing Oral Agents Insulin 4.5 M* Insulin only Absent Obesity/Diabetes Disease Progression * US diabetes population – 2001 ** Ford ES et al. JAMA 2002;287;356-359.

  28. BASIC RESEARCHKeys to Success • Find the right preceptor/environment Compatible Diverse – MDs, PhDs, others Supportive • Identify the project that is interesting to you • Spend the necessary time training Other labs Learn as many techniques as possible • Learn how to write! • Persevere and be patient

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